Neoplasm, Advanced or Metastatic
Conditions
Keywords
Drug therapy
Brief summary
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).
Detailed description
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: * Sequence A: TAK-117 capsules (9\*100 mg) first then TAK-117 tablets (3\*300 mg) * Sequence B: TAK-117 tablets (3\*300 mg) first then TAK-117 capsules (9\*100 mg) 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).
Interventions
DRUGLansoprazole
Lansoprazole capsules
DRUGTAK-117
TAK-117 capsules
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Is aged 18 to 45 years inclusive, at the time of consent. 2. Is healthy adult male or female. 3. Weighs greater than or equal to (\>=) 45 kilogram (kg) (female) or \>=55 kg (male), and body mass index (BMI) between 18.0 and 30.0 kilogram per square meter (kg/m\^2), inclusive, at screening. 4. Suitable venous access for the study-required blood sampling, including PK sampling. 5. Has provided the voluntary written consent.
Exclusion criteria
1. Any clinically significant abnormality at screening or medical history of cardiac, hepatic, renal, respiratory, gastrointestinal (GI), endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease. 2. Manifestations of malabsorption due to prior GI surgery, GI disease, or for an unknown other reason that may alter the PK of TAK-117 or lansoprazole. 3. Creatinine clearance less than or equal to (\<=) 90 milliliter per minute (mL/min) based either on Cockroft-Gault estimate or based on a 12- or 24-hour urine collection during screening. 4. Known intolerance to TAK-117 or lansoprazole, or any of the excipients of either drug. 5. A positive test result for human immunodeficiency virus (HIV), hepatitis A antibody (HAVAb), hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibody Anti-HBc (IgM), or hepatitis C antibody (HCVAb) tests at screening, or serological reactions for syphilis during screening. 6. Has Lactose intolerance (only for Part 2).
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | 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 |
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 08 January 2016 to 22 July 2016.
Pre-assignment details
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 by arm
| Arm | Count |
|---|---|
| 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). | 11 |
| 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). | 9 |
| 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). | 8 |
| 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). | 10 |
| 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. | 16 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| First Intervention (Day 1) | Adverse Event | 2 | 1 | 0 | 0 | 0 |
| First Intervention (Day 1) | Other | 0 | 0 | 1 | 0 | 0 |
| First Intervention (Day 1) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part-1: TAK-117 900 mg Capsules + TAK-117 900 mg Tablets | Total | Part-3: TAK-117 900 mg + Lansoprazole 30 mg | Part-2: TAK-117 600 mg Fed + TAK-117 600 mg Fasted | Part-2: TAK-117 600 mg Fasted + TAK-117 600 mg Fed | Part-1: TAK-117 900 mg Tablets + TAK-117 900 mg Capsules |
|---|---|---|---|---|---|---|
| Age, Customized 18-45 years | 11 participants 7.63 | 54 participants | 16 participants 6.88 | 10 participants 6.13 | 8 participants 7.15 | 9 participants 7.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 24 Participants | 6 Participants | 4 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 30 Participants | 10 Participants | 6 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 19 Participants | 8 Participants | 3 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 29 Participants | 5 Participants | 7 Participants | 4 Participants | 5 Participants |
| Region of Enrollment United States | 11 participants | 54 participants | 16 participants | 10 participants | 8 participants | 9 participants |
| Sex: Female, Male Female | 8 Participants | 38 Participants | 9 Participants | 10 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 16 Participants | 7 Participants | 0 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 19 | 5 / 18 | 8 / 17 | 4 / 17 | 6 / 16 | 1 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 19 | 0 / 18 | 0 / 17 | 0 / 17 | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117
Time frame: 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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part-1: TAK-117 900 mg Capsules (9*100 mg Capsules) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 64165.340 ng*hr/mL | Geometric Coefficient of Variation 77 |
| Part-1: TAK-117 900 mg Tablets (3*300 mg Tablets) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 96293.083 ng*hr/mL | Geometric Coefficient of Variation 77 |
| Part-2: TAK-117 600 mg Fasted (2*300 mg Tablets) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 81595.634 ng*hr/mL | Geometric Coefficient of Variation 61 |
| Part-2: TAK-117 600 mg Fed (2*300 mg Tablets) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 128336.896 ng*hr/mL | Geometric Coefficient of Variation 39 |
| Part-3: TAK-117 900 mg (3*300 mg Tablets) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 85782.122 ng*hr/mL | Geometric Coefficient of Variation 85 |
| Part-3: TAK-117 900 mg (3*300 mg Tablets) + Lansoprazole 30 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 6547.254 ng*hr/mL | Geometric Coefficient of Variation 66 |
Comparison: Analysis of variance was performed for calculating 90 % CIs for the ratios of log-transformed geometric mean AUC∞ of TAK-117 tablet versus capsule dosage form.90% CI: [0.93, 2.51]
Comparison: Analysis of variance was performed for calculating 90% CIs for the ratios of log-transformed geometric mean AUC∞ of TAK-117 tablet dosage form with food versus without food.90% CI: [1, 2.25]
Comparison: Analysis of variance was performed for calculating 90% CIs for the ratios of log-transformed geometric mean AUC∞ of TAK-117 tablet dosage form with lansoprazole versus a single dose of TAK-117 alone.90% CI: [0.03, 0.18]
Primary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117
Time frame: 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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part-1: TAK-117 900 mg Capsules (9*100 mg Capsules) | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117 | 45727.280 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 94 |
| Part-1: TAK-117 900 mg Tablets (3*300 mg Tablets) | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117 | 66015.952 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 91 |
| Part-2: TAK-117 600 mg Fasted (2*300 mg Tablets) | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117 | 71442.968 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 67 |
| Part-2: TAK-117 600 mg Fed (2*300 mg Tablets) | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117 | 127143.511 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 39 |
| Part-3: TAK-117 900 mg (3*300 mg Tablets) | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117 | 63165.064 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 91 |
| Part-3: TAK-117 900 mg (3*300 mg Tablets) + Lansoprazole 30 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117 | 1018.650 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 129 |
Comparison: Analysis of variance was performed for calculating 90 % CIs for the ratios of log-transformed geometric mean AUClast of TAK-117 tablet versus capsule dosage form.90% CI: [0.98, 2.18]
Comparison: Analysis of variance was performed for calculating 90% CIs for the ratios of log-transformed geometric mean AUClast of TAK-117 tablet dosage form with food versus without food.90% CI: [1.11, 2.78]
Comparison: Analysis of variance was performed for calculating 90% CIs for the ratios of log-transformed geometric mean AUClast of TAK-117 tablet dosage form with lansoprazole versus a single dose of TAK-117 alone.90% CI: [0.01, 0.04]
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-117
Time frame: 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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part-1: TAK-117 900 mg Capsules (9*100 mg Capsules) | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 4632.992 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 71 |
| Part-1: TAK-117 900 mg Tablets (3*300 mg Tablets) | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 6225.347 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 53 |
| Part-2: TAK-117 600 mg Fasted (2*300 mg Tablets) | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 6455.111 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| Part-2: TAK-117 600 mg Fed (2*300 mg Tablets) | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 7847.591 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| Part-3: TAK-117 900 mg (3*300 mg Tablets) | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 5859.156 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 58 |
| Part-3: TAK-117 900 mg (3*300 mg Tablets) + Lansoprazole 30 mg | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 190.172 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 144 |
Comparison: Analysis of variance was performed for calculating 90 percent (%) confidence intervals (CIs) for the ratios of log-transformed geometric mean Cmax of TAK-117 tablet versus capsule dosage form.90% CI: [1, 1.83]
Comparison: 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.90% CI: [0.86, 1.67]
Comparison: 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.90% CI: [0.02, 0.07]
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part-1: TAK-117 900 mg Capsules (9*100 mg Capsules) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 2.067 hours |
| Part-1: TAK-117 900 mg Tablets (3*300 mg Tablets) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 3.000 hours |
| Part-2: TAK-117 600 mg Fasted (2*300 mg Tablets) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 3.000 hours |
| Part-2: TAK-117 600 mg Fed (2*300 mg Tablets) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 6.033 hours |
| Part-3: TAK-117 900 mg (3*300 mg Tablets) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 3.000 hours |
| Part-3: TAK-117 900 mg (3*300 mg Tablets) + Lansoprazole 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 3.517 hours |
Secondary
Part 1: Renal Clearance (CLr) of TAK-117
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-1: TAK-117 900 mg Capsules (9*100 mg Capsules) | Part 1: Renal Clearance (CLr) of TAK-117 | 0.314 liter per hour (L/hr) | Standard Deviation 0.1179 |
| Part-1: TAK-117 900 mg Tablets (3*300 mg Tablets) | Part 1: Renal Clearance (CLr) of TAK-117 | 0.311 liter per hour (L/hr) | Standard Deviation 0.1304 |