Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to assess the BA of 30 or 60 milligram (mg) dexlansoprazole capsule manufactured at TOB (Takeda GmbH Plant Oranienburg) to the corresponding 30 or 60 mg dexlansoprazole manufactured at TPC (Takeda Pharmaceutical Company Ltd.).
Detailed description
The drug being tested in this study is called dexlansoprazole. Dexlansoprazole is being tested in healthy participants to compare the BA of dexlansoprazole capsules manufactured by TOB relative to dexlansoprazole capsules manufactured by TPC, under fed conditions. The study consists of two parts: Part 1 participants will receive dexlansoprazole 30 mg capsules manufactured by TOB and TPC in a crossover fashion; Part 2 participants will receive dexlansoprazole 60 mg capsules manufactured by TOB and TPC in a crossover fashion. The study will enroll approximately 120 participants. Participants will be randomly assigned (by chance, like flipping a coin) to 1 of the 4 treatment sequences as following: * Part 1: Dexlansoprazole 30 mg (TOB) + Dexlansoprazole 30 mg (TPC) * Part 1: Dexlansoprazole 30 mg (TPC) + Dexlansoprazole 30 mg (TOB) * Part 2: Dexlansoprazole 60 mg (TOB) + Dexlansoprazole 60 mg (TPC) * Part 2: Dexlansoprazole 60 mg (TPC) + Dexlansoprazole 60 mg (TOB) All participants will be asked to take capsule of assigned dexlansoprazole on Day 1, 30 minutes following the beginning of a high-fat/high calorie breakfast of each treatment period. This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 86 days. Participants will be contacted by phone call approximately 10 days after the last dose of study drug for a follow-up assessment.
Interventions
Dexlansoprazole delayed-release capsules.
Dexlansoprazole delayed-release capsules.
Dexlansoprazole delayed-release capsules.
Dexlansoprazole delayed-release capsules.
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. Has a body mass index (BMI) from 18 to 30 kilogram per square meter (kg/m\^2), at Screening. 2. Is willing and able to consume the high-fat/high-calorie breakfast administered during the study.
Exclusion criteria
1. Has a history of drug abuse (defined as any illicit drug use) or drug addiction in the 12 months prior to Screening or a history of alcohol abuse (defined as regular consumption exceeding 21 units per week \[1 unit equal (=) 12 ounces (oz) beer, 1.5 oz hard liquor, or 5 oz wine\]) within 1 year prior to the Screening Visit, or is unwilling to agree to abstain from alcohol and drugs throughout the study. 2. Has a positive test result for drugs of abuse (defined as any illicit drug use) or alcohol at Screening or Check-in (Day -1 of Period 1). 3. Has received any known hepatic or renal clearance altering agents (example, erythromycin, cimetidine, barbiturates, phenothiazines, fluvoxamine, etc) for a period of 28 days prior to Day 1 of Period 1. 4. Has donated blood products (such as plasma) within 30 days or has donated whole blood or lost 450 milliliter (mL) or more of his or her blood volume, or had a transfusion of any blood product within 56 days prior to Day 1 of Period 1. 5. With the exception of acetaminophen, the subject has taken any excluded medication, supplements, or food products or beverages containing grapefruit or grapefruit juice, star fruit or star fruit juice, Seville-type (sour) oranges and marmalade, apple, orange, or pineapple juice, vegetables from the mustard green family (example, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard), and charbroiled meats. Hormonal contraception and hormone replacement therapy are allowed, as long as the subject has been on a stable dose for a minimum of 90 days prior to Day 1 of Period 1. 6. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch nicotine gum, e-cigarettes) within 28 days prior to Check-in (Day -1 of Period 1), or has a positive cotinine test at Screening or Check-in (Day -1 of Period 1), or is unwilling to abstain from these products for the duration of the study. 7. Has received dexlansoprazole or lansoprazole in a previous clinical study or as a therapeutic agent within 6 months of screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole | Day 1 pre-dose and at multiple time points (up to 24 hours) post dose |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Dexlansoprazole | Day 1 pre-dose and at multiple time points (up to 24 hours) post dose |
| AUC0_infobs: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for Dexlansoprazole | Day 1 pre-dose and at multiple time points (up to 24 hours) post dose |
| AUC0_infpred: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Predicted Value of the Last Quantifiable Concentration for Dexlansoprazole | Day 1 pre-dose and at multiple time points (up to 24 hours) post dose |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 10 January 2019 to 09 April 2019.
Pre-assignment details
Healthy participants were enrolled in this 2-part and 2-way crossover study to receive dexlansoprazole 30 milligram (mg) capsules manufactured by Takeda GmbH Plant Oranienburg (TOB) and 30 mg capsules manufactured by Takeda Pharmaceutical Company Ltd. (TPC) in Part 1 and dexlansoprazole 60 mg capsules by TOB and 60 mg capsules by TPC in Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Dexlansoprazole 30 mg TOB + Dexlansoprazole 30 mg TPC Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5-day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2. | 31 |
| Part 1: Dexlansoprazole 30 mg TPC + Dexlansoprazole 30 mg TOB Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2. | 31 |
| Part 2: Dexlansoprazole 60 mg TOB + Dexlansoprazole 60 mg TPC Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2. | 30 |
| Part 2: Dexlansoprazole 60 mg TPC + Dexlansoprazole 60 mg TOB Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2. | 30 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-Up (12 Days) | Lost to Follow-up | 0 | 1 | 1 | 0 |
| Period 1 (2 Days) | Adverse Event | 1 | 1 | 0 | 0 |
| Washout Period (at Least 5 Days) | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Washout Period (at Least 5 Days) | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: Dexlansoprazole 30 mg TOB + Dexlansoprazole 30 mg TPC | Part 1: Dexlansoprazole 30 mg TPC + Dexlansoprazole 30 mg TOB | Part 2: Dexlansoprazole 60 mg TOB + Dexlansoprazole 60 mg TPC | Part 2: Dexlansoprazole 60 mg TPC + Dexlansoprazole 60 mg TOB | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 31 Participants | 30 Participants | 30 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 25 Participants | 24 Participants | 23 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 6 Participants | 6 Participants | 7 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 6 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 | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 30 Participants | 29 Participants | 25 Participants | 27 Participants | 111 Participants |
| Region of Enrollment United States | 31 Participants | 31 Participants | 30 Participants | 30 Participants | 122 Participants |
| Sex: Female, Male Female | 19 Participants | 18 Participants | 15 Participants | 17 Participants | 69 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 15 Participants | 13 Participants | 53 Participants |
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 / 61 | 0 / 61 | 0 / 59 | 0 / 59 |
| other Total, other adverse events | 4 / 61 | 3 / 61 | 7 / 59 | 5 / 59 |
| serious Total, serious adverse events | 0 / 61 | 0 / 61 | 0 / 59 | 0 / 59 |
Outcome results
Primary
AUC0_infobs: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for Dexlansoprazole
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post dose
Population: PK evaluable set: participants enrolled into study, received at least one dose of study drug, were not discontinued from study and replaced with other participants, completed PK sampling in both periods, complied sufficiently with protocol, displayed evaluable PK profiles. PK analysis population where data at specified time points was available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dexlansoprazole 30 mg TOB | AUC0_infobs: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for Dexlansoprazole | 2927 ng*hour/mL | Geometric Coefficient of Variation 66.2 |
| Part 1: Dexlansoprazole 30 mg TPC | AUC0_infobs: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for Dexlansoprazole | 2885 ng*hour/mL | Geometric Coefficient of Variation 63.9 |
| Part 2: Dexlansoprazole 60 mg TOB | AUC0_infobs: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for Dexlansoprazole | 6734 ng*hour/mL | Geometric Coefficient of Variation 60.3 |
| Part 2: Dexlansoprazole 60 mg TPC | AUC0_infobs: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for Dexlansoprazole | 6220 ng*hour/mL | Geometric Coefficient of Variation 56.8 |
90% CI: [1.0186, 1.0933]
90% CI: [1.0027, 1.0929]
Primary
AUC0_infpred: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Predicted Value of the Last Quantifiable Concentration for Dexlansoprazole
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post dose
Population: PK evaluable set: participants enrolled into study, received at least one dose of study drug, were not discontinued from study and replaced with other participants, completed PK sampling in both periods, complied sufficiently with protocol, displayed evaluable PK profiles. PK analysis population where data at specified time points was available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dexlansoprazole 30 mg TOB | AUC0_infpred: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Predicted Value of the Last Quantifiable Concentration for Dexlansoprazole | 2926 ng*hour/mL | Geometric Coefficient of Variation 66.2 |
| Part 1: Dexlansoprazole 30 mg TPC | AUC0_infpred: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Predicted Value of the Last Quantifiable Concentration for Dexlansoprazole | 2884 ng*hour/mL | Geometric Coefficient of Variation 63.9 |
| Part 2: Dexlansoprazole 60 mg TOB | AUC0_infpred: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Predicted Value of the Last Quantifiable Concentration for Dexlansoprazole | 6733 ng*hour/mL | Geometric Coefficient of Variation 60.3 |
| Part 2: Dexlansoprazole 60 mg TPC | AUC0_infpred: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Predicted Value of the Last Quantifiable Concentration for Dexlansoprazole | 6217 ng*hour/mL | Geometric Coefficient of Variation 56.8 |
90% CI: [1.0188, 1.0935]
90% CI: [1.0029, 1.0934]
Primary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Dexlansoprazole
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post dose
Population: The PK evaluable set included all participants who enrolled into study and received at least one dose of study drug, were not discontinued from study and replaced with other participants, who completed PK sampling in both periods, complied sufficiently with protocol, and displayed evaluable PK profiles.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dexlansoprazole 30 mg TOB | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Dexlansoprazole | 2881 nanogram*hour per milliliter(ng*hour/mL) | Geometric Coefficient of Variation 66.8 |
| Part 1: Dexlansoprazole 30 mg TPC | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Dexlansoprazole | 2756 nanogram*hour per milliliter(ng*hour/mL) | Geometric Coefficient of Variation 62.8 |
| Part 2: Dexlansoprazole 60 mg TOB | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Dexlansoprazole | 6608 nanogram*hour per milliliter(ng*hour/mL) | Geometric Coefficient of Variation 58.5 |
| Part 2: Dexlansoprazole 60 mg TPC | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Dexlansoprazole | 6278 nanogram*hour per milliliter(ng*hour/mL) | Geometric Coefficient of Variation 59.4 |
90% CI: [1.007, 1.0855]
90% CI: [1.0192, 1.1046]
Primary
Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post dose
Population: The pharmacokinetic (PK) evaluable set included all participants who enrolled into study and received at least one dose of study drug, were not discontinued from study and replaced with other participants, who completed PK sampling in both periods, complied sufficiently with protocol, and displayed evaluable PK profiles.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dexlansoprazole 30 mg TOB | Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole | 610.1 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 52 |
| Part 1: Dexlansoprazole 30 mg TPC | Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole | 622.5 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 49.9 |
| Part 2: Dexlansoprazole 60 mg TOB | Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole | 1381 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 45.3 |
| Part 2: Dexlansoprazole 60 mg TPC | Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole | 1302 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 50.3 |
90% CI: [0.9171, 1.0473]
90% CI: [1.0025, 1.1501]