Healthy Volunteers
Conditions
Brief summary
A study to compare the pharmacokinetics and food-effect bioavailability of sprinkle formulation of lubiprostone, as compared to lubiprostone capsules in healthy volunteers.
Detailed description
To compare the pharmacokinetics of the sprinkle formulation of lubiprostone, as compared to lubiprostone capsules and to determine the effect of food on the bioavailability and plasma pharmacokinetics of lubiprostone sprinkle.
Interventions
DRUGCohort 1: Lubiprostone Capsule, Fasted
Lubiprostone soft gelatin capsule administered under fasted conditions
DRUGCohort 1: Lubiprostone Sprinkle Formulation, Fasted
Lubiprostone sprinkle formulation administered under fasted conditions
DRUGCohort 2: Lubiprostone Sprinkle Formulation, Fed
Lubiprostone sprinkle formulation administered under fed conditions
DRUGCohort 2: Lubiprostone Sprinkle Formulation, Fasted
Lubiprostone sprinkle formulation administered under fasted conditions
Sponsors
Takeda
Sucampo Pharma Americas, LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Is male or female, between 18 and 55 years of age, inclusive. * Has a 12-lead electrocardiogram (ECG) within normal limits and is in good health based upon review of medical history, physical examination results, vital signs (within normal range), and normal laboratory profile for both blood and urine.
Exclusion criteria
* Has an active or recent history of alcoholism or drug addiction (within 1 year prior) * Is a smoker or has a recent history of smoking (within 6 months) * Routinely consumes food known to alter drug metabolism (i.e., grapefruit juice, coffee, tea, cola, chocolate, cocoa, or other caffeine or methyl-xanthine containing foods or beverages) and/or cannot refrain from these items * Has donated blood within 3 months * Has a medical/surgical condition that might interfere with the absorption, distribution, metabolism, or excretion of the study medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohort 1: Area Under the Concentration-time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t) of M3 Metabolite | 1 day |
| Cohort 1: Maximum Observed Concentration (Cmax) of M3 Metabolite | 1 day |
Secondary
| Measure | Time frame |
|---|---|
| Cohort 2: Total Exposure (AUC0-t) of M3 With Administration of Sprinkle Lubiprostone Under Fed Versus (vs) Fasted Condition | 1 day |
| Cohort 2: Maximum Observed Concentration (Cmax) of M3 Metabolite in Fed vs Fasted Conditions | 1 day |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From the first dose of study drug up to 28 days | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is any untoward medical occurrence that results in death;is life-threatening;requires inpatient hospitalization or prolongation of present hospitalization;results in persistent or significant disability/incapacity;is a congenital anomaly/birth defect;or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. |
Countries
United States
Participant flow
Recruitment details
All participants were recruited in the United States
Pre-assignment details
Treatment periods for Cohorts 1 and 2 did not have the same participants. Participants in each cohort were randomized to sequence. In each sequence the first treatment was given for 14 days, there was a 7-day washout period, and then the second treatment was given for 14 days.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Treatment A Then Treatment B Participants in Cohort 1 who received Treatment A: Lubiprostone Capsule, Fasted for 14 days, followed (after a 7-day washout) by Treatment B: Sprinkle Formulation, Fasted for 14 days | 18 |
| Cohort 1: Treatment B Then Treatment A Participants in Cohort 1 who received Treatment B: Sprinkle Formulation, Fasted for 14 days, followed (after a 7-day washout) by Treatment A: Lubiprostone Capsule, Fasted for 14 days | 17 |
| Cohort 2: Treatment C Then Treatment D Participants in Cohort 2 who received Treatment C: Sprinkle, Fed for 14 days, followed (after a 7-day washout) by Treatment D: Sprinkle Formulation, Fasted for 14 days | 7 |
| Cohort 2: Treatment D Then Treatment C Participants in Cohort 2 who received Treatment D: Sprinkle Formulation, Fasted for 14 days, followed (after a 7-day washout) by Treatment C: Sprinkle, Fed for 14 days | 7 |
| Total | 49 |
Baseline characteristics
| Characteristic | Cohort 1: Treatment A Then Treatment B | Cohort 1: Treatment B Then Treatment A | Cohort 2: Treatment C Then Treatment D | Cohort 2: Treatment D Then Treatment C | 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 | 18 Participants | 17 Participants | 7 Participants | 7 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 9 Participants | 3 Participants | 2 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 8 Participants | 4 Participants | 5 Participants | 23 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 12 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 14 Participants | 4 Participants | 3 Participants | 36 Participants |
| Region of Enrollment United States | 18 participants | 17 participants | 7 participants | 7 participants | 49 participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 4 Participants | 4 Participants | 27 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 3 Participants | 3 Participants | 22 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 / 31 | 0 / 35 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 13 / 31 | 23 / 35 | 6 / 14 | 6 / 14 |
| serious Total, serious adverse events | 0 / 31 | 0 / 35 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Cohort 1: Area Under the Concentration-time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t) of M3 Metabolite
Time frame: 1 day
Population: PK population, defined as those with plasma concentration of lubiprostone or M3 sufficient to calculate at least 1 PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Lubiprostone Capsule, Fasted | Cohort 1: Area Under the Concentration-time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t) of M3 Metabolite | 117.518 h*pg/mL | Geometric Coefficient of Variation 57.56 |
| Treatment B: Sprinkle Formulation, Fasted | Cohort 1: Area Under the Concentration-time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t) of M3 Metabolite | 163.615 h*pg/mL | Geometric Coefficient of Variation 47.45 |
90% CI: [1.166, 1.782]
Primary
Cohort 1: Maximum Observed Concentration (Cmax) of M3 Metabolite
Time frame: 1 day
Population: Evaluable PK Population included all participants in the PK Population who had sufficient plasma drug concentration data of either lubiprostone or M3 to calculate at least 1 evaluable PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Lubiprostone Capsule, Fasted | Cohort 1: Maximum Observed Concentration (Cmax) of M3 Metabolite | 63.463 pg/mL | Geometric Coefficient of Variation 55.56 |
| Treatment B: Sprinkle Formulation, Fasted | Cohort 1: Maximum Observed Concentration (Cmax) of M3 Metabolite | 127.729 pg/mL | Geometric Coefficient of Variation 61.32 |
90% CI: [1.615, 2.589]
Secondary
Cohort 2: Maximum Observed Concentration (Cmax) of M3 Metabolite in Fed vs Fasted Conditions
Time frame: 1 day
Population: PK Evaluable Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Lubiprostone Capsule, Fasted | Cohort 2: Maximum Observed Concentration (Cmax) of M3 Metabolite in Fed vs Fasted Conditions | 48.192 pg/mL | Geometric Coefficient of Variation 30.52 |
| Treatment B: Sprinkle Formulation, Fasted | Cohort 2: Maximum Observed Concentration (Cmax) of M3 Metabolite in Fed vs Fasted Conditions | 116.815 pg/mL | Geometric Coefficient of Variation 31.93 |
90% CI: [0.339, 0.502]
Secondary
Cohort 2: Total Exposure (AUC0-t) of M3 With Administration of Sprinkle Lubiprostone Under Fed Versus (vs) Fasted Condition
Time frame: 1 day
Population: PK Evaluable Population.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Lubiprostone Capsule, Fasted | Cohort 2: Total Exposure (AUC0-t) of M3 With Administration of Sprinkle Lubiprostone Under Fed Versus (vs) Fasted Condition | 135.805 h*pg/mL | Geometric Coefficient of Variation 58.17 |
| Treatment B: Sprinkle Formulation, Fasted | Cohort 2: Total Exposure (AUC0-t) of M3 With Administration of Sprinkle Lubiprostone Under Fed Versus (vs) Fasted Condition | 152.900 h*pg/mL | Geometric Coefficient of Variation 26.96 |
90% CI: [0.675, 1.168]
Other Pre-specified
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is any untoward medical occurrence that results in death;is life-threatening;requires inpatient hospitalization or prolongation of present hospitalization;results in persistent or significant disability/incapacity;is a congenital anomaly/birth defect;or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
Time frame: From the first dose of study drug up to 28 days
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Lubiprostone Capsule, Fasted | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 13 Participants |
| Treatment A: Lubiprostone Capsule, Fasted | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 0 Participants |
| Treatment B: Sprinkle Formulation, Fasted | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 0 Participants |
| Treatment B: Sprinkle Formulation, Fasted | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 23 Participants |
| Treatment C: Sprinkle Formulation, Fed | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 6 Participants |
| Treatment C: Sprinkle Formulation, Fed | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 0 Participants |
| Treatment D: Sprinkle Formulation, Fasted | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 6 Participants |
| Treatment D: Sprinkle Formulation, Fasted | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 0 Participants |