Trial Outcomes & Findings for Comparative Pharmacokinetics and Food-Effect Bioavailability of Lubiprostone Sprinkle in Healthy Volunteers (NCT NCT03010631)
NCT ID: NCT03010631
Last Updated: 2020-03-09
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
49 participants
Primary outcome timeframe
1 day
Results posted on
2020-03-09
Participant Flow
All participants were recruited in the United States
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.
Participant milestones
| Measure |
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
|
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
|
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
|
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
|
|---|---|---|---|---|
|
Cohort 1
STARTED
|
18
|
17
|
0
|
0
|
|
Cohort 1
COMPLETED
|
14
|
17
|
0
|
0
|
|
Cohort 1
NOT COMPLETED
|
4
|
0
|
0
|
0
|
|
Cohort 2
STARTED
|
0
|
0
|
7
|
7
|
|
Cohort 2
COMPLETED
|
0
|
0
|
7
|
7
|
|
Cohort 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Comparative Pharmacokinetics and Food-Effect Bioavailability of Lubiprostone Sprinkle in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Cohort 1: Treatment A Then Treatment B
n=18 Participants
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
|
Cohort 1: Treatment B Then Treatment A
n=17 Participants
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
|
Cohort 2: Treatment C Then Treatment D
n=7 Participants
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
|
Cohort 2: Treatment D Then Treatment C
n=7 Participants
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
|
Total
n=49 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
49 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
36 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
17 participants
n=7 Participants
|
7 participants
n=5 Participants
|
7 participants
n=4 Participants
|
49 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 1 dayPopulation: PK population, defined as those with plasma concentration of lubiprostone or M3 sufficient to calculate at least 1 PK parameter
Outcome measures
| Measure |
Treatment A: Lubiprostone Capsule, Fasted
n=31 Participants
Participants in the pharmacokinetic-evaluable (PK) population who received treatment A
|
Treatment B: Sprinkle Formulation, Fasted
n=31 Participants
Participants in the PK population who received treatment B
|
Treatment C: Sprinkle Formulation, Fed
Cohort 2 participants who received Treatment C
|
Treatment D: Sprinkle Formulation, Fasted
Cohort 2 participants who received Treatment D
|
|---|---|---|---|---|
|
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
|
163.615 h*pg/mL
Geometric Coefficient of Variation 47.45
|
—
|
—
|
PRIMARY outcome
Timeframe: 1 dayPopulation: 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.
Outcome measures
| Measure |
Treatment A: Lubiprostone Capsule, Fasted
n=31 Participants
Participants in the pharmacokinetic-evaluable (PK) population who received treatment A
|
Treatment B: Sprinkle Formulation, Fasted
n=31 Participants
Participants in the PK population who received treatment B
|
Treatment C: Sprinkle Formulation, Fed
Cohort 2 participants who received Treatment C
|
Treatment D: Sprinkle Formulation, Fasted
Cohort 2 participants who received Treatment D
|
|---|---|---|---|---|
|
Cohort 1: Maximum Observed Concentration (Cmax) of M3 Metabolite
|
63.463 pg/mL
Geometric Coefficient of Variation 55.56
|
127.729 pg/mL
Geometric Coefficient of Variation 61.32
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 dayPopulation: PK Evaluable Population.
Outcome measures
| Measure |
Treatment A: Lubiprostone Capsule, Fasted
n=14 Participants
Participants in the pharmacokinetic-evaluable (PK) population who received treatment A
|
Treatment B: Sprinkle Formulation, Fasted
n=14 Participants
Participants in the PK population who received treatment B
|
Treatment C: Sprinkle Formulation, Fed
Cohort 2 participants who received Treatment C
|
Treatment D: Sprinkle Formulation, Fasted
Cohort 2 participants who received Treatment D
|
|---|---|---|---|---|
|
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
|
152.900 h*pg/mL
Geometric Coefficient of Variation 26.96
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 dayPopulation: PK Evaluable Population.
Outcome measures
| Measure |
Treatment A: Lubiprostone Capsule, Fasted
n=14 Participants
Participants in the pharmacokinetic-evaluable (PK) population who received treatment A
|
Treatment B: Sprinkle Formulation, Fasted
n=14 Participants
Participants in the PK population who received treatment B
|
Treatment C: Sprinkle Formulation, Fed
Cohort 2 participants who received Treatment C
|
Treatment D: Sprinkle Formulation, Fasted
Cohort 2 participants who received Treatment D
|
|---|---|---|---|---|
|
Cohort 2: Maximum Observed Concentration (Cmax) of M3 Metabolite in Fed vs Fasted Conditions
|
48.192 pg/mL
Geometric Coefficient of Variation 30.52
|
116.815 pg/mL
Geometric Coefficient of Variation 31.93
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From the first dose of study drug up to 28 daysPopulation: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Lubiprostone Capsule, Fasted
n=31 Participants
Participants in the pharmacokinetic-evaluable (PK) population who received treatment A
|
Treatment B: Sprinkle Formulation, Fasted
n=35 Participants
Participants in the PK population who received treatment B
|
Treatment C: Sprinkle Formulation, Fed
n=14 Participants
Cohort 2 participants who received Treatment C
|
Treatment D: Sprinkle Formulation, Fasted
n=14 Participants
Cohort 2 participants who received Treatment D
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse Events
|
13 Participants
|
23 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Serious Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Treatment A
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Treatment B
Serious events: 0 serious events
Other events: 23 other events
Deaths: 0 deaths
Treatment C
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Treatment D
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=31 participants at risk
All participants who received lubiprostone 2x24 μg capsule once orally.
|
Treatment B
n=35 participants at risk
All participants who received lubiprostone 2x24 μg sprinkle formulation once orally.
|
Treatment C
n=14 participants at risk
All participants who received lubiprostone 2x24 μg sprinkle formulation once orally under fed conditions.
|
Treatment D
n=14 participants at risk
All participants who received lubiprostone 2x24 μg sprinkle formulation once orally under fasted conditions.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
16.1%
5/31 • From first dose of study drug up to 28 days
|
28.6%
10/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
|
Gastrointestinal disorders
Diarrhoea
|
29.0%
9/31 • From first dose of study drug up to 28 days
|
28.6%
10/35 • From first dose of study drug up to 28 days
|
14.3%
2/14 • From first dose of study drug up to 28 days
|
21.4%
3/14 • From first dose of study drug up to 28 days
|
|
Gastrointestinal disorders
Abdominal pain
|
9.7%
3/31 • From first dose of study drug up to 28 days
|
14.3%
5/35 • From first dose of study drug up to 28 days
|
7.1%
1/14 • From first dose of study drug up to 28 days
|
14.3%
2/14 • From first dose of study drug up to 28 days
|
|
Gastrointestinal disorders
Eructation
|
6.5%
2/31 • From first dose of study drug up to 28 days
|
8.6%
3/35 • From first dose of study drug up to 28 days
|
14.3%
2/14 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/31 • From first dose of study drug up to 28 days
|
11.4%
4/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/31 • From first dose of study drug up to 28 days
|
5.7%
2/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
|
Gastrointestinal disorders
Flatulence
|
3.2%
1/31 • From first dose of study drug up to 28 days
|
5.7%
2/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/31 • From first dose of study drug up to 28 days
|
5.7%
2/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
|
Nervous system disorders
Headache
|
12.9%
4/31 • From first dose of study drug up to 28 days
|
14.3%
5/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
14.3%
2/14 • From first dose of study drug up to 28 days
|
|
Nervous system disorders
Dizziness
|
3.2%
1/31 • From first dose of study drug up to 28 days
|
20.0%
7/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
14.3%
2/14 • From first dose of study drug up to 28 days
|
|
Nervous system disorders
Presyncope
|
6.5%
2/31 • From first dose of study drug up to 28 days
|
0.00%
0/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
|
Cardiac disorders
Postural orthostatic tachycardia syndrome
|
9.7%
3/31 • From first dose of study drug up to 28 days
|
5.7%
2/35 • From first dose of study drug up to 28 days
|
7.1%
1/14 • From first dose of study drug up to 28 days
|
7.1%
1/14 • From first dose of study drug up to 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.5%
2/31 • From first dose of study drug up to 28 days
|
5.7%
2/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
|
Vascular disorders
Flushing
|
0.00%
0/31 • From first dose of study drug up to 28 days
|
5.7%
2/35 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
0.00%
0/14 • From first dose of study drug up to 28 days
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/31 • From first dose of study drug up to 28 days
|
0.00%
0/35 • From first dose of study drug up to 28 days
|
7.1%
1/14 • From first dose of study drug up to 28 days
|
7.1%
1/14 • From first dose of study drug up to 28 days
|
Additional Information
Medical Information Call Center
Mallinckrodt Pharmaceuticals
Phone: 800-556-3314
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER