Gastrointestinal Agents

All Drugs and Chemicals

Lansoprazole

Dexlansoprazole

Serabelisib

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Enzyme Inhibitors

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.

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.

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.

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.

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.

TAK-117

Medical Director

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:

* 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).

A Study to Evaluate the Relative Bioavailability, Effect of Food, and Gastric Potential Hydrogen (pH) Modification on the Pharmacokinetics of TAK-117 (MLN1117) in Healthy Participants

A Phase 1, Open-Label Study to Evaluate the Relative Bioavailability, Effect of Food, and Gastric pH Modification on the Pharmacokinetics of MLN1117 in Healthy Subjects

Millennium Pharmaceuticals, Inc.

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.

TAK-117 9\*100 mg, capsules (CTM), orally, once on Day 1 or 15 of intervention period.

Part-1: TAK-117 900 mg Capsules

TAK-117 3\*300 mg, tablets (NTM), orally, once on Day 1 or 15 of intervention period.

Part-1: TAK-117 900 mg Tablets

TAK-117 2\*300 mg, tablets (NTM), orally, once in a fasted state on Day 1 or 15 of intervention period.

Part-2: TAK-117 600 mg Fasted

TAK-117 2\*300 mg, tablets (NTM), orally, with a standard high-fat breakfast, once on Day 1 or 15 of intervention period.

Part-2: TAK-117 600 mg Fed

TAK-117 3\*300 mg, tablets (NTM), orally, once on Day 1.

Part-3: TAK-117 900 mg

Lansoprazole 30 mg, capsule, orally, once daily from Day 10 to Day 14.

Part-3: Lansoprazole 30 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.

Part 3: Lansoprazole 30 mg + TAK-117 900 mg

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).

Part-1: TAK-117 900 mg Capsules + TAK-117 900 mg Tablets

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).

Part-1: TAK-117 900 mg Tablets + TAK-117 900 mg Capsules

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).

Part-2: TAK-117 600 mg Fasted + TAK-117 600 mg Fed

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).

Part-2: TAK-117 600 mg Fed + TAK-117 600 mg Fasted

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.

Part-3: TAK-117 900 mg + Lansoprazole 30 mg

Total

18-45 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Safety analysis population included all the participants who received at least 1 dose of study drug.

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.

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.

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.

Part-1: TAK-117 900 mg Capsules (9*100 mg Capsules)

Part-1: TAK-117 900 mg Tablets (3*300 mg Tablets)

Part-2: TAK-117 600 mg Fasted (2*300 mg Tablets)

Part-2: TAK-117 600 mg Fed (2*300 mg Tablets)

Part-3: TAK-117 900 mg (3*300 mg Tablets)

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-3: TAK-117 900 mg (3*300 mg Tablets) + Lansoprazole 30 mg

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.

Cmax: Maximum Observed Plasma 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.

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117

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.

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.

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.

AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117

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.

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.

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.

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.

Spots Global Cancer Trial Database for neoplasm, advanced or metastatic