Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to assess the bioavailability of dexlansoprazole from a 30 milligram (mg) or 60 mg delayed-release capsule manufactured at Takeda GmbH Plant Oranienburg, Germany (TOB) relative to that of dexlansoprazole from a 30 mg or 60 mg capsule manufactured at Takeda Pharmaceutical Company Ltd. (Osaka, Japan) (TPC).
Detailed description
The drug being tested in this study is called dexlansoprazole. This study will compare bioavailability of dexlansoprazole from 30 mg and 60 mg dexlansoprazole delayed release capsules manufactured at TOB relative to the corresponding 30 mg and 60 mg dexlansoprazole delayed release capsules manufactured at TPC. The study will enroll approximately 104 participants. Participants will be randomly assigned (by chance, like flipping a coin) to 1 of the 4 treatment sequences: * Dexlansoprazole 30 mg TOB followed by Dexlansoprazole 30 mg TPC * Dexlansoprazole 30 mg TPC followed by Dexlansoprazole 30 mg TOB * Dexlansoprazole 60 mg TOB followed by Dexlansoprazole 60 mg TPC * Dexlansoprazole 60 mg TPC followed by Dexlansoprazole 60 mg TOB All participants will be asked to take single oral dose of dexlansoprazole at the same time on Day 1 of each Period. This single center trial will be conducted in the United States. The overall time to participate in this study is 18 days. Participants will visit the clinic on Day -1 and remained confined until Day 2 of Period 1 and 2. A washout period of minimum 5 days will be maintained between the doses in each Period. Participants will be contacted by telephone 10 (+/-2) days after the last dose of study drug for a follow-up assessment.
Interventions
Dexlansoprazole delayed-release.
Dexlansoprazole delayed-release.
Dexlansoprazole delayed-release.
Dexlansoprazole delayed-release.
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. Healthy men and women aged 18 to 55 years old, inclusive, with a body mass index between 18 and 30 kilogram per square meter (kg/m\^2), inclusive. 2. Who are capable of understanding and complying with protocol requirements. 3. Must be in good health as determined by a physician based upon medical history, vital signs, electrocardiogram (ECG), and physical examination. 4. Must have clinical chemistry, hematology, and complete urinalysis (after fasting for at least 8 hours) at Screening and Check-in (Day -1 of Period 1) results within the reference range for the testing laboratory unless the out-of-range results are deemed not clinically significant by the investigator. 5. Must sign a written informed consent form (ICF) prior to initiation of study procedures.
Exclusion criteria
1. Has a history of significant gastrointestinal (GI) disorders manifested with persistent, chronic or intermittent nausea, vomiting, diarrhea, or has a current or recent (within 6 months) GI disease that would influence the absorption of drugs (example, a history of malabsorption, severe esophageal reflux, peptic ulcer disease or erosive esophagitis (EE) with frequent \[more than once per week\] occurrence of heartburn). 2. Has consumed medications, certain foods, and supplements, including prescription and over-the-counter medications, within the protocol-specified time periods prior to Check-in (Day -1 of Period 1), or is unwilling to agree to abstain from these products. 3. Have received dexlansoprazole in a previous clinical study or as a therapeutic agent within 6 months of Screening, 4. Have a known hypersensitivity to any component of the formulation of dexlansoprazole capsules or other drugs with the same mechanism of action (including lansoprazole, omeprazole, rabeprazole, pantoprazole, or esomeprazole), or related compounds. 5. Any significant results from physical examination or clinical laboratory results that make the participant unsuitable for the study.
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 |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity 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 25 April 2017 to 31 July 2017.
Pre-assignment details
Healthy participants were enrolled in this 2 part study to receive dexlansoprazole 30 milligram (mg) capsules manufactured by Takeda GmbH Plant (Oranienburg, Germany) (TOB) or 30 mg capsules manufactured by Takeda Pharmaceutical Company Ltd. (Osaka, Japan) (TPC) in Part 1 and dexlansoprazole 60 mg capsules by TOB or 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 on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast. | 28 |
| Part 1: Dexlansoprazole 30 mg TPC + Dexlansoprazole 30 mg TOB Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast. | 28 |
| Part 2: Dexlansoprazole 60 mg TOB+ Dexlansoprazole 60 mg TPC Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast. | 30 |
| Part 2: Dexlansoprazole 60 mg TPC+ Dexlansoprazole 60 mg TOB Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast. | 30 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Intervention Period 2 (2 Days) | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Intervention Period 2 (2 Days) | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Washout Period (at Least 5 Days) | Adverse Event | 1 | 0 | 0 | 1 |
| Washout Period (at Least 5 Days) | Lost to Follow-up | 0 | 3 | 2 | 3 |
| Washout Period (at Least 5 Days) | Other | 0 | 0 | 2 | 0 |
| Washout Period (at Least 5 Days) | Withdrawal by Subject | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: Dexlansoprazole 30 mg TOB+ Dexlansoprazole 30 mg TPC | Total | Part 2: Dexlansoprazole 60 mg TPC+ Dexlansoprazole 60 mg TOB | Part 2: Dexlansoprazole 60 mg TOB+ Dexlansoprazole 60 mg TPC | Part 1: Dexlansoprazole 30 mg TPC + Dexlansoprazole 30 mg TOB |
|---|---|---|---|---|---|
| Age, Continuous | 30.0 Years STANDARD_DEVIATION 7.95 | 29.0 Years STANDARD_DEVIATION 8.81 | 28.4 Years STANDARD_DEVIATION 9.71 | 29.2 Years STANDARD_DEVIATION 7.78 | 28.5 Years STANDARD_DEVIATION 9.98 |
| Alcohol Classification Current Drinker | 5 participants | 30 participants | 11 participants | 8 participants | 6 participants |
| Alcohol Classification Former Drinker | 4 participants | 12 participants | 1 participants | 4 participants | 3 participants |
| Alcohol Classification Never Drank | 19 participants | 74 participants | 18 participants | 18 participants | 19 participants |
| Body mass index (BMI) | 24.7 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.59 | 24.5 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.82 | 24.5 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.33 | 24.6 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.65 | 24.4 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.75 |
| Caffeine Consumption Had caffeine consumption | 15 participants | 70 participants | 22 participants | 18 participants | 15 participants |
| Caffeine Consumption Had no caffeine consumption | 13 participants | 46 participants | 8 participants | 12 participants | 13 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 17 Participants | 1 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 97 Participants | 29 Participants | 25 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 4 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 1 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 | 26 Participants | 103 Participants | 25 Participants | 28 Participants | 24 Participants |
| Region of Enrollment United States | 28 Participants | 116 Participants | 30 Participants | 30 Participants | 28 Participants |
| Sex: Female, Male Female | 11 Participants | 49 Participants | 14 Participants | 14 Participants | 10 Participants |
| Sex: Female, Male Male | 17 Participants | 67 Participants | 16 Participants | 16 Participants | 18 Participants |
| Smoking Classification Current Smoker | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Smoking Classification Former Smoker | 4 participants | 9 participants | 2 participants | 3 participants | 0 participants |
| Smoking Classification Never Smoked | 24 participants | 107 participants | 28 participants | 27 participants | 28 participants |
| Xanthine Consumption Had no xanthine consumption | 13 participants | 46 participants | 8 participants | 12 participants | 13 participants |
| Xanthine Consumption Had xanthine consumption | 15 participants | 70 participants | 22 participants | 18 participants | 15 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 / 51 | 0 / 55 | 0 / 55 | 0 / 56 |
| other Total, other adverse events | 8 / 51 | 9 / 55 | 8 / 55 | 11 / 56 |
| serious Total, serious adverse events | 0 / 51 | 0 / 55 | 0 / 55 | 0 / 56 |
Outcome results
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Dexlansoprazole
Time frame: Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration. PK analysis set where data at specified time points was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexlansoprazole 30 mg TOB | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Dexlansoprazole | 2579.6 ng*hour/mL | Standard Deviation 2760.38 |
| Dexlansoprazole 30 mg TPC | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Dexlansoprazole | 2420.6 ng*hour/mL | Standard Deviation 2322.58 |
| Dexlansoprazole 60 mg TOB | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Dexlansoprazole | 5746.2 ng*hour/mL | Standard Deviation 4785.72 |
| Dexlansoprazole 60 mg TPC | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Dexlansoprazole | 5630.4 ng*hour/mL | Standard Deviation 5527.34 |
p-value: 0.416390% CI: [0.9733, 1.0975]ANOVA
p-value: 0.977890% CI: [0.9458, 1.0638]ANOVA
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 set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 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 | 2416.3 nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 2280.91 |
| 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 | 2327.6 nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 2052.94 |
| 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 | 5715.5 nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 4521.84 |
| 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 | 5684.7 nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 5361.88 |
p-value: 0.320990% CI: [0.9792, 1.1024]ANOVA
p-value: 0.389690% CI: [0.9719, 1.1029]ANOVA
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) set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexlansoprazole 30 mg TOB | Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole | 515.7 nanogram/milliliter (ng/mL) | Standard Deviation 257.6 |
| Dexlansoprazole 30 mg TPC | Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole | 519.5 nanogram/milliliter (ng/mL) | Standard Deviation 305.66 |
| Dexlansoprazole 60 mg TOB | Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole | 1027.0 nanogram/milliliter (ng/mL) | Standard Deviation 598.74 |
| Dexlansoprazole 60 mg TPC | Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole | 978.6 nanogram/milliliter (ng/mL) | Standard Deviation 581.34 |
p-value: 0.553590% CI: [0.9453, 1.1521]ANOVA
p-value: 0.89290% CI: [0.9334, 1.1113]ANOVA