Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The main aim of this study is to check what the body of a healthy adult who either fasted or had eaten does to TAK-721 and how TAK-721 is distributed in and removed from the body. Other aims are to learn how safe the treatment with TAK-721 is and how suitable the TAK-721 is for healthy adults who either fasted or had eaten. All participants will receive TAK-721 but half will be assigned by chance to the participant group who are fasting first then getting the high-fat/high-calorie meal later or the group who gets meal first and fasts later. The group assignment will be switched once during the course of the study so that all participants will receive TAK-721 in both a fasted or fed condition.
Detailed description
The drug being tested in this study is called budesonide. Budesonide oral suspension (BOS) is being tested in healthy adult participants. This study will determine whether the absorption of BOS will be altered if taken with food. The study will enroll approximately 20 patients. The study will consist of two treatment sequences and two periods separated by a washout period of 2 days. Participants will be randomly assigned (by chance, like flipping a fair coin) to one of the two treatment sequences: * Treatment Sequence 1: Participants will receive 2 mg BOS orally on Day 1 of Period 1 in fasted condition (Treatment A). Two days later, participants will receive 2 mg BOS orally on Day 1 of Period 2 in fed condition (Treatment B). * Treatment Sequence 2: Participants will receive 2 mg BOS orally on Day 1 of Period 1 in fed condition (Treatment B). Two days later, participants will receive 2 mg BOS orally on Day 1 of Period 2 in fasted condition (Treatment A). This single center trial will be conducted in the United States. Participation in the study is up to approximately 34 days. Participants will visit the clinic approximately three days after last dose of study drug for a follow-up assessment.
Interventions
DRUGBudesonide
Budesonide oral suspension
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Continuous non-smoker who has not used nicotine- and tobacco-containing products for at least 3 months prior to the first dosing based on participant self-reporting. 2. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meters squared (kg/m\^2) at the screening visit.
Exclusion criteria
1. Presence of any active infection at the screening visit or check-in. 2. Positive urine drug or alcohol results at the screening visit or check-in. 3. Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at the screening visit. 4. Participant is unable to refrain from or anticipates the use of: 1. Any drugs, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing. Medication listed as part of acceptable birth control methods, hormone replacement therapy, and thyroid hormone replacement medication will be allowed. 2. Any drugs known to be moderate or strong inducers of cytochrome P450 (CYP) 3A4 enzymes and/or p-glycoprotein (P-gp), including St. John's Wort, for 28 days prior to the first dosing. Appropriate sources (e.g., Flockhart Table™) will be consulted to confirm lack of pharmacokinetic (PK) /pharmacodynamic interaction with the study drug. 5. Participant is lactose intolerant. 6. Donation of blood or significant blood loss within 56 days prior to the first dosing. 7. Plasma donation within 7 days prior to the first dosing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Concentration (Cmax) of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 |
| Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 |
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC∞) of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time 0 to 12 Hours (AUC0-12) of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 12 hours) post-dose on Day 1 | — |
| Area Under the Curve From the Last Quantifiable Concentration to Infinity Expressed as a Percentage of AUC∞ (AUCextrap%) of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 | — |
| Time to First Occurrence of Cmax (Tmax) of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 | — |
| Lag Time to First Quantifiable Concentration (Tlag) of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 | — |
| Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE), and Death | From first dose of study drug up to the end of study (EOS) (Up to 15 days) | An adverse event (AE) was 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 AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug. An SAE was defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that may require an intervention to prevent above items and expose the participant to danger. |
| Terminal Disposition Phase Rate Constant (λz) of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 | — |
| Apparent Clearance (CL/F) of BOS Calculated Using the Observed Value of the Last Quantifiable Concentration of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 | — |
| Apparent Volume of Distribution During the Terminal Disposition Phase (Vz/F) of BOS Calculated Using the Observed Value of the Last Quantifiable Concentration of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 | — |
| Terminal Disposition Phase Half-life (t1/2z) of BOS | Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1 | — |
| Number of Participants With Clinically Significant Abnormal Vital Sign Values Reported as Adverse Events | From first dose of study drug up to EOS (Up to 15 days) | Vital signs included body temperature, respiratory rate, blood pressure, and pulse rate evaluations. |
| Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values Reported as Adverse Events | From first dose of study drug up to EOS (Up to 15 days) | Clinical laboratory parameters included hematology, clinical chemistry, serum immunoglobulin and urinalysis tests. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 6 February 2023 to 20 February 2023.
Pre-assignment details
Healthy participants were enrolled to receive budesonide oral suspension (BOS) in either of the 2 treatment sequences Fasted-Fed or Fed-Fasted.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: BOS 2 mg Fasted, Then Fed Participants received 2 mg BOS, single dose, orally on Day 1 of Period 1 under fasted condition (Treatment A). After a washout of at least 2 days participants then received 2 mg BOS single dose, orally on Day 1 of Period 2 under fed condition (Treatment B). | 10 |
| Sequence 2: BOS 2 mg Fed, Then Fasted Participants received 2 mg BOS, single dose, orally on Day 1 of Period 1 under fed condition (Treatment B). After a washout of at least 2 days participants received 2 mg BOS single dose, orally on Day 1 of Period 2 under fasted condition (Treatment A). | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Sequence 1: BOS 2 mg Fasted, Then Fed | Sequence 2: BOS 2 mg Fed, Then Fasted | Total |
|---|---|---|---|
| Age, Continuous | 38.6 years STANDARD_DEVIATION 9.5 | 32.7 years STANDARD_DEVIATION 9.97 | 35.7 years STANDARD_DEVIATION 9.95 |
| Body Mass Index (BMI) | 27.52 kilograms per metre square (kg/m^2) STANDARD_DEVIATION 2.91 | 27.59 kilograms per metre square (kg/m^2) STANDARD_DEVIATION 2.706 | 27.56 kilograms per metre square (kg/m^2) STANDARD_DEVIATION 2.735 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 9 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 165.4 centimetres (cm) STANDARD_DEVIATION 10.71 | 169.0 centimetres (cm) STANDARD_DEVIATION 11.52 | 167.2 centimetres (cm) STANDARD_DEVIATION 10.98 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 8 Participants |
| Weight | 75.99 kilograms (kg) STANDARD_DEVIATION 15.39 | 79.51 kilograms (kg) STANDARD_DEVIATION 14.53 | 77.75 kilograms (kg) STANDARD_DEVIATION 14.68 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 2 / 20 | 5 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC∞) of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: BOS 2 mg Fasted | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC∞) of BOS | 3075 pg*h/mL | Geometric Coefficient of Variation 57 |
| Treatment B: BOS 2 mg Fed | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC∞) of BOS | 3892 pg*h/mL | Geometric Coefficient of Variation 47.1 |
Primary
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: BOS 2 mg Fasted | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of BOS | 2811 picograms*hours per milliliter (pg*h/mL) | Geometric Coefficient of Variation 57.5 |
| Treatment B: BOS 2 mg Fed | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of BOS | 3529 picograms*hours per milliliter (pg*h/mL) | Geometric Coefficient of Variation 52.1 |
Primary
Maximum Observed Concentration (Cmax) of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: Pharmacokinetic (PK) Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: BOS 2 mg Fasted | Maximum Observed Concentration (Cmax) of BOS | 692.9 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 54.4 |
| Treatment B: BOS 2 mg Fed | Maximum Observed Concentration (Cmax) of BOS | 604.1 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 46.6 |
Secondary
Apparent Clearance (CL/F) of BOS Calculated Using the Observed Value of the Last Quantifiable Concentration of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: BOS 2 mg Fasted | Apparent Clearance (CL/F) of BOS Calculated Using the Observed Value of the Last Quantifiable Concentration of BOS | 650.4 liters per hour (L/h) | Geometric Coefficient of Variation 57 |
| Treatment B: BOS 2 mg Fed | Apparent Clearance (CL/F) of BOS Calculated Using the Observed Value of the Last Quantifiable Concentration of BOS | 513.9 liters per hour (L/h) | Geometric Coefficient of Variation 47.1 |
Secondary
Apparent Volume of Distribution During the Terminal Disposition Phase (Vz/F) of BOS Calculated Using the Observed Value of the Last Quantifiable Concentration of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: BOS 2 mg Fasted | Apparent Volume of Distribution During the Terminal Disposition Phase (Vz/F) of BOS Calculated Using the Observed Value of the Last Quantifiable Concentration of BOS | 3967 liters (L) | Geometric Coefficient of Variation 45 |
| Treatment B: BOS 2 mg Fed | Apparent Volume of Distribution During the Terminal Disposition Phase (Vz/F) of BOS Calculated Using the Observed Value of the Last Quantifiable Concentration of BOS | 3513 liters (L) | Geometric Coefficient of Variation 32.9 |
Secondary
Area Under the Concentration-time Curve From Time 0 to 12 Hours (AUC0-12) of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 12 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: BOS 2 mg Fasted | Area Under the Concentration-time Curve From Time 0 to 12 Hours (AUC0-12) of BOS | 2728 pg*h/mL | Geometric Coefficient of Variation 53 |
| Treatment B: BOS 2 mg Fed | Area Under the Concentration-time Curve From Time 0 to 12 Hours (AUC0-12) of BOS | 3208 pg*h/mL | Geometric Coefficient of Variation 42.2 |
Secondary
Area Under the Curve From the Last Quantifiable Concentration to Infinity Expressed as a Percentage of AUC∞ (AUCextrap%) of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: BOS 2 mg Fasted | Area Under the Curve From the Last Quantifiable Concentration to Infinity Expressed as a Percentage of AUC∞ (AUCextrap%) of BOS | 7.275 percentage of AUC | Geometric Coefficient of Variation 61.7 |
| Treatment B: BOS 2 mg Fed | Area Under the Curve From the Last Quantifiable Concentration to Infinity Expressed as a Percentage of AUC∞ (AUCextrap%) of BOS | 7.126 percentage of AUC | Geometric Coefficient of Variation 75.6 |
Secondary
Lag Time to First Quantifiable Concentration (Tlag) of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: BOS 2 mg Fasted | Lag Time to First Quantifiable Concentration (Tlag) of BOS | 0.328 hours |
| Treatment B: BOS 2 mg Fed | Lag Time to First Quantifiable Concentration (Tlag) of BOS | 0.308 hours |
Secondary
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE), and Death
An adverse event (AE) was 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 AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug. An SAE was defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that may require an intervention to prevent above items and expose the participant to danger.
Time frame: From first dose of study drug up to the end of study (EOS) (Up to 15 days)
Population: Safety Set included all participants who received any study drug. Data is presented per fed or fasted condition.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: BOS 2 mg Fasted | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE), and Death | TEAEs | 2 Participants |
| Treatment A: BOS 2 mg Fasted | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE), and Death | SAEs | 0 Participants |
| Treatment A: BOS 2 mg Fasted | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE), and Death | Deaths | 0 Participants |
| Treatment B: BOS 2 mg Fed | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE), and Death | Deaths | 0 Participants |
| Treatment B: BOS 2 mg Fed | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE), and Death | TEAEs | 5 Participants |
| Treatment B: BOS 2 mg Fed | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE), and Death | SAEs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values Reported as Adverse Events
Clinical laboratory parameters included hematology, clinical chemistry, serum immunoglobulin and urinalysis tests.
Time frame: From first dose of study drug up to EOS (Up to 15 days)
Population: Safety Set included all participants who received any study drug. Data is presented per fed or fasted condition.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: BOS 2 mg Fasted | Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values Reported as Adverse Events | 0 Participants |
| Treatment B: BOS 2 mg Fed | Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values Reported as Adverse Events | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormal Vital Sign Values Reported as Adverse Events
Vital signs included body temperature, respiratory rate, blood pressure, and pulse rate evaluations.
Time frame: From first dose of study drug up to EOS (Up to 15 days)
Population: Safety Set included all participants who received any study drug. Data is presented per fed or fasted condition.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: BOS 2 mg Fasted | Number of Participants With Clinically Significant Abnormal Vital Sign Values Reported as Adverse Events | 0 Participants |
| Treatment B: BOS 2 mg Fed | Number of Participants With Clinically Significant Abnormal Vital Sign Values Reported as Adverse Events | 0 Participants |
Secondary
Terminal Disposition Phase Half-life (t1/2z) of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: BOS 2 mg Fasted | Terminal Disposition Phase Half-life (t1/2z) of BOS | 4.270 hours |
| Treatment B: BOS 2 mg Fed | Terminal Disposition Phase Half-life (t1/2z) of BOS | 5.096 hours |
Secondary
Terminal Disposition Phase Rate Constant (λz) of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: BOS 2 mg Fasted | Terminal Disposition Phase Rate Constant (λz) of BOS | 0.1627 1/hour |
| Treatment B: BOS 2 mg Fed | Terminal Disposition Phase Rate Constant (λz) of BOS | 0.1362 1/hour |
Secondary
Time to First Occurrence of Cmax (Tmax) of BOS
Time frame: Periods 1 and 2: Pre-dose and at multiple timepoints (up to 24 hours) post-dose on Day 1
Population: PK Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: BOS 2 mg Fasted | Time to First Occurrence of Cmax (Tmax) of BOS | 1.286 hours (h) |
| Treatment B: BOS 2 mg Fed | Time to First Occurrence of Cmax (Tmax) of BOS | 2.516 hours (h) |