Ignite Creation Date:
2024-05-06 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 1:55 PM
Study NCT ID:
NCT04735822
Status:
COMPLETED
Last Update Posted:
2022-05-11
First Post:
2021-01-13
Brief Title:
A Phase I Study to Evaluate the Taste of Belumosudil Oral Suspensions Assess Relative Bioavailability
Sponsor:
Kadmon Corporation LLC
Organization:
Kadmon Corporation LLC
Study Overview
Official Title:
A 2-Part Phase I Study to Evaluate the Taste Profile of Belumosudil Oral Suspensions Assess Relative Bioavailability of the Selected Belumosudil Oral Suspension Formulation Compared With Oral Tablets in Healthy Male Subjects
Status:
COMPLETED
Status Verified Date:
2022-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a single-center randomized open-label 2-part study in healthy male subjects to evaluate the taste profile of different belumosudil oral suspensions and the relative bioavailability of those chosen oral suspensions of belumosudil compared to oral tablets of belumosudil
Part 1 is an open-label randomized single-period study of oral suspensions of belumosudil 40 mgmL delivered in 6 different vehicles Approximately 12 healthy male subjects 2 subjects in each of 6 groups will be administered a single dose of belumosudil 40 mgmL in 6 different vehicles Vehicles 1 2 3 4 5 and 6 in corresponding Regimens A B C D E and F in different sequences of the 6 vehicles All subjects will receive 1 dose of all belumosudil in all 6 vehicles which are as follows ABFCED BCADFE CDBEAF DECFBA EFDACB and FAEBDC
Part 2 is a single-center open-label randomized 3-period design to assess the relative bioavailability of a selected belumosudil suspension formulation compared to the oral belumosudil Tablet reference and the effect of food on the selected belumosudil suspension formulation in 18 healthy male subjects Subjects will be randomized prior to the administration of the first dose of IMP to 1 of 6 treatment sequences GHI HIG IGH IHG GIH and HGI with 3 subjects assigned to each treatment sequence where
Regimen G--oral belumosudil 200 mg tablet reference with the subject fed Regimen H--belumosudil powder 200 mg for oral suspension or belumosudil 200 mg oral suspension with the subject fasting and Regimen I--belumosudil 200 mg powder for oral suspension or belumosudil 200 mg oral suspension with the subject fed
Part 1 is an open-label randomized single-period study of oral suspensions of belumosudil 40 mgmL delivered in 6 different vehicles Approximately 12 healthy male subjects 2 subjects in each of 6 groups will be administered a single dose of belumosudil 40 mgmL in 6 different vehicles Vehicles 1 2 3 4 5 and 6 in corresponding Regimens A B C D E and F in different sequences of the 6 vehicles All subjects will receive 1 dose of all belumosudil in all 6 vehicles which are as follows ABFCED BCADFE CDBEAF DECFBA EFDACB and FAEBDC
Part 2 is a single-center open-label randomized 3-period design to assess the relative bioavailability of a selected belumosudil suspension formulation compared to the oral belumosudil Tablet reference and the effect of food on the selected belumosudil suspension formulation in 18 healthy male subjects Subjects will be randomized prior to the administration of the first dose of IMP to 1 of 6 treatment sequences GHI HIG IGH IHG GIH and HGI with 3 subjects assigned to each treatment sequence where
Regimen G--oral belumosudil 200 mg tablet reference with the subject fed Regimen H--belumosudil powder 200 mg for oral suspension or belumosudil 200 mg oral suspension with the subject fasting and Regimen I--belumosudil 200 mg powder for oral suspension or belumosudil 200 mg oral suspension with the subject fed
Detailed Description:
PART 1
This is a single center open-label randomized single period design to assess the taste profile of different novel regimens from bottles containing 1200 mg of belumosudil Twelve healthy subjects will receive single doses of the 6 bottled oral formulations
Regimen A belumosudil 40 mgmL delivered by Vehicle 1 sterile water for irrigation Regimen B belumosudil 40 mgmL delivered by Vehicle 2 low sucralose solution Regimen C belumosudil 40 mgmL delivered by Vehicle 3 high sucralose solution Regimen D belumosudil 40 mgmL delivered by Vehicle 4 orange flavor with low sucralose solution Regimen E belumosudil 40 mgmL delivered by Vehicle 5 tropical fruit blend with low sucralose solution Regimen F belumosudil 40 mgmL delivered by Vehicle 6 lemon flavor with low sucralose solution
Subjects will sip the belumosudil oral suspension and then spit it out The maximum dose is belumosudil 200 mg
On Day 1 two subjects each will be randomized to 1 of 6 treatment sequences with belumosudil
ABFCED 2 subjects BCADFE 2 subjects CDBEAF 2 subjects DECFBA 2 subjects EFDACB 2 subjects FAEBDC 2 subjects
Subjects will undergo preliminary screening procedures to determine their eligibility for Part 1 of the study at a screening visit Day -28 to Day -2 of Part 1 Subjects will be admitted to the clinical unit on the morning prior to investigational medicinal product IMP administration Day -1 for confirmation of eligibility and baseline procedures Prior to the first administration of IMP either Day -1 or prior to the completion of breakfast pre-dose on Day 1 subjects will be given a training questionnaire using an example fluid eg orange juicesquash
In the evening of Day -1 subjects will receive a light snack and will then fast from all food and drink except water Following the overnight fast approximately 8 hours subjects will consume a standard breakfast Following breakfast subjects will brush their teeth using tap water toothpaste will not be permitted The first dose of IMP will be administered approximately 2 hours after breakfast has been completed
Subjects will receive the test belumosudil from bottles in regimens according to a randomization schedule Each regimen will follow the same study design Subjects will receive a single dose of belumosudil 40 mgmL as an oral suspension which will be held in the mouth for approximately 1 minute before it is expectorated and will subsequently complete a written tastepalatability questionnaire individually and privately No belumosudil is to be consumed
There will be a washout period of 30 min 10 min minimum 20 min between tasting each regimen inclusive of palate cleansing During this time subjects will cleanse their palates using tap water administered freely in 50 mL aliquots and unsalted crackers before further tasting It is expected that all regimens will be tasted on the same day
A single plasma pharmacokinetic PK sample will be taken approximately 1 hour post-final dose prior to discharge from the clinical unit This sample will be retained and only analyzed in case of accidental swallowing of the formulation by a subject andor for the purpose of investigating a possible treatment-emergent adverse event TEAE related to the IMP
Subjects will remain on site until 1 hour post-final tastepalatability assessment To ensure the ongoing well-being of the subjects a follow-up phone call will take place 3 to 7 days after the final dose If a subject reports any adverse events AEs after discharge which is a cause for concern they will be required to attend the clinical unit for a follow-up assessment This follow-up visit will be considered an unscheduled visit
Following the completion of Part 1 an interim data review will be performed during which the tastepalatability assessment data will be reviewed to determine the flavor system that will be incorporated into the IMP formulation for administration in Part 2
PART 2
This is a single-center open-label randomized 3-period design to assess the relative bioavailability of a selected belumosudil suspension formulation from Part 1 compared to the belumosudil oral tablet Eighteen subjects will receive single doses of the following
Regimen G 200 mg belumosudil tablet reference drug orally when subjects are fed Regimen H 200 mg belumosudil powder for oral suspension or belumosudil oral suspension when subjects are fasting and Regimen I 200 mg belumosudil powder for oral suspension or belumosudil oral suspension when subjects are fed
On Day 1 three subjects each will be randomized to 1 of 6 treatment sequences with belumosudil
GHI 3 subjects HIG 3 subjects IGH 3 subjects IHG 3 subjects GIH 3 subjects HGI 3 subjects
Subjects will undergo preliminary screening procedures to determine their eligibility for Part 2 of the study at a screening visit Day -28 to Day -2 of Part 2 Subjects who have taken part in Part 1 of the study are permitted to take part in Part 2
Each study period will follow a similar design Subjects will be admitted to the clinical unit on the morning prior to the first IMP administration Day -1 of Period 1 for confirmation of eligibility and baseline procedures For Regimen H only subjects will be given a training questionnaire using an example fluid eg orange juicesquash prior to IMP administration This will be performed either on Day -1 only applicable if Regimen H is administered in Period 2 or 3 or prior to the completion of breakfast pre-dose on Day 1
Subjects will receive a single dose of IMP in the morning of Day 1 following an overnight fast of a minimum of 10 hours Regimen H fasted state or following a standard breakfast Regimens G and I fed state Blood samples will be collected at regular intervals for PK analysis Following administration of Regimen H subjects will complete a written tastepalatability questionnaire individually and privately
Subjects will reside in the clinical unit for 10 consecutive nights that will cover all 3 treatment periods All subjects will remain on site until 72 h post-final dose for safety and PK assessments There will be a minimum washout period of 3 days between each IMP administration To ensure the ongoing well-being of the subjects a follow-up phone call will take place 3 to 7 days after the final dose If a subject reports any AEs after discharge which is a cause for concern they will be required to attend the clinical unit for a follow-up assessment This follow-up visit will be considered an unscheduled visit
This is a single center open-label randomized single period design to assess the taste profile of different novel regimens from bottles containing 1200 mg of belumosudil Twelve healthy subjects will receive single doses of the 6 bottled oral formulations
Regimen A belumosudil 40 mgmL delivered by Vehicle 1 sterile water for irrigation Regimen B belumosudil 40 mgmL delivered by Vehicle 2 low sucralose solution Regimen C belumosudil 40 mgmL delivered by Vehicle 3 high sucralose solution Regimen D belumosudil 40 mgmL delivered by Vehicle 4 orange flavor with low sucralose solution Regimen E belumosudil 40 mgmL delivered by Vehicle 5 tropical fruit blend with low sucralose solution Regimen F belumosudil 40 mgmL delivered by Vehicle 6 lemon flavor with low sucralose solution
Subjects will sip the belumosudil oral suspension and then spit it out The maximum dose is belumosudil 200 mg
On Day 1 two subjects each will be randomized to 1 of 6 treatment sequences with belumosudil
ABFCED 2 subjects BCADFE 2 subjects CDBEAF 2 subjects DECFBA 2 subjects EFDACB 2 subjects FAEBDC 2 subjects
Subjects will undergo preliminary screening procedures to determine their eligibility for Part 1 of the study at a screening visit Day -28 to Day -2 of Part 1 Subjects will be admitted to the clinical unit on the morning prior to investigational medicinal product IMP administration Day -1 for confirmation of eligibility and baseline procedures Prior to the first administration of IMP either Day -1 or prior to the completion of breakfast pre-dose on Day 1 subjects will be given a training questionnaire using an example fluid eg orange juicesquash
In the evening of Day -1 subjects will receive a light snack and will then fast from all food and drink except water Following the overnight fast approximately 8 hours subjects will consume a standard breakfast Following breakfast subjects will brush their teeth using tap water toothpaste will not be permitted The first dose of IMP will be administered approximately 2 hours after breakfast has been completed
Subjects will receive the test belumosudil from bottles in regimens according to a randomization schedule Each regimen will follow the same study design Subjects will receive a single dose of belumosudil 40 mgmL as an oral suspension which will be held in the mouth for approximately 1 minute before it is expectorated and will subsequently complete a written tastepalatability questionnaire individually and privately No belumosudil is to be consumed
There will be a washout period of 30 min 10 min minimum 20 min between tasting each regimen inclusive of palate cleansing During this time subjects will cleanse their palates using tap water administered freely in 50 mL aliquots and unsalted crackers before further tasting It is expected that all regimens will be tasted on the same day
A single plasma pharmacokinetic PK sample will be taken approximately 1 hour post-final dose prior to discharge from the clinical unit This sample will be retained and only analyzed in case of accidental swallowing of the formulation by a subject andor for the purpose of investigating a possible treatment-emergent adverse event TEAE related to the IMP
Subjects will remain on site until 1 hour post-final tastepalatability assessment To ensure the ongoing well-being of the subjects a follow-up phone call will take place 3 to 7 days after the final dose If a subject reports any adverse events AEs after discharge which is a cause for concern they will be required to attend the clinical unit for a follow-up assessment This follow-up visit will be considered an unscheduled visit
Following the completion of Part 1 an interim data review will be performed during which the tastepalatability assessment data will be reviewed to determine the flavor system that will be incorporated into the IMP formulation for administration in Part 2
PART 2
This is a single-center open-label randomized 3-period design to assess the relative bioavailability of a selected belumosudil suspension formulation from Part 1 compared to the belumosudil oral tablet Eighteen subjects will receive single doses of the following
Regimen G 200 mg belumosudil tablet reference drug orally when subjects are fed Regimen H 200 mg belumosudil powder for oral suspension or belumosudil oral suspension when subjects are fasting and Regimen I 200 mg belumosudil powder for oral suspension or belumosudil oral suspension when subjects are fed
On Day 1 three subjects each will be randomized to 1 of 6 treatment sequences with belumosudil
GHI 3 subjects HIG 3 subjects IGH 3 subjects IHG 3 subjects GIH 3 subjects HGI 3 subjects
Subjects will undergo preliminary screening procedures to determine their eligibility for Part 2 of the study at a screening visit Day -28 to Day -2 of Part 2 Subjects who have taken part in Part 1 of the study are permitted to take part in Part 2
Each study period will follow a similar design Subjects will be admitted to the clinical unit on the morning prior to the first IMP administration Day -1 of Period 1 for confirmation of eligibility and baseline procedures For Regimen H only subjects will be given a training questionnaire using an example fluid eg orange juicesquash prior to IMP administration This will be performed either on Day -1 only applicable if Regimen H is administered in Period 2 or 3 or prior to the completion of breakfast pre-dose on Day 1
Subjects will receive a single dose of IMP in the morning of Day 1 following an overnight fast of a minimum of 10 hours Regimen H fasted state or following a standard breakfast Regimens G and I fed state Blood samples will be collected at regular intervals for PK analysis Following administration of Regimen H subjects will complete a written tastepalatability questionnaire individually and privately
Subjects will reside in the clinical unit for 10 consecutive nights that will cover all 3 treatment periods All subjects will remain on site until 72 h post-final dose for safety and PK assessments There will be a minimum washout period of 3 days between each IMP administration To ensure the ongoing well-being of the subjects a follow-up phone call will take place 3 to 7 days after the final dose If a subject reports any AEs after discharge which is a cause for concern they will be required to attend the clinical unit for a follow-up assessment This follow-up visit will be considered an unscheduled visit
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2020-003446-37 | EUDRACT_NUMBER | None | None |