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This study comprised of 2 parts, Part A and Part B. Part B will only be conducted if the relative bioavailability of the tablet formulation was at least 70% of the capsule formulation.
Part A is a randomized, single-dose, 4-period, 4-way cross-over study to evaluate the effect of food on the TP 3654 capsule and assess the relative bioavailability of the TP-3654 capsule versus tablet formulations. Following a screening period of up to 28 days, eligible participants will be admitted to the clinical research unit (CRU) on Day -1. Participants will fast overnight from Day -1 to Day 1. On Day 1, participants will be randomly assigned to a treatment sequence, and they will receive TP-3654 per their assigned sequence.
Part B is a randomized, single-dose, 3-period, 3-way cross-over study to evaluate the effect of food on the PK of the TP-3654 tablet formulation. Following a screening period of up to 28 days, eligible participants will be admitted to the CRU on Day -1. As with Part A, participants will fast overnight from Day -1 to Day 1. On Day 1, they will be randomly assigned to a treatment sequence, and they will receive TP-3654 per their assigned sequence.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A - Sequence 1 | Experimental | Following a screening period of up to 28 days, eligible participants will be admitted to the clinical research unit on Day -1. Participants will fast overnight from Day -1 to Day 1. On Day 1, participants randomly assigned to Sequence 1 will take TP 3654 with or without food as follows: Day 1 - 480mg (4 x 120mg capsules) once daily with low fat meal, Day 4 - 480mg (4 x 120mg capsules) once daily fasted, Day 7 - 480mg (4 x 120mg capsules) once daily with high fat meal, and Day 10 - 480mg (2 x 240mg tablets) once daily fasted. |
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| Part A - Sequence 2 | Experimental | Following a screening period of up to 28 days, eligible participants will be admitted to the clinical research unit on Day -1. Participants will fast overnight from Day -1 to Day 1. On Day 1, participants randomly assigned to Sequence 2 will take TP 3654 with or without food as follows: Day 1 - 480mg (4 x 120mg capsules) once daily fasted, Day 4 - 480mg (2 x 240mg tablets) once daily fasted, Day 7 - 480mg (4 x 120mg capsules) once daily with low fat meal, and Day 10 - 480mg (4 x 120mg capsules) once daily with high fat meal. |
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| Part A - Sequence 3 | Experimental | Following a screening period of up to 28 days, eligible participants will be admitted to the clinical research unit on Day -1. Participants will fast overnight from Day -1 to Day 1. On Day 1, participants randomly assigned to Sequence 3 will take TP 3654 with or without food as follows: Day 1 - 480mg (2 x 240mg tablets) once daily fasted, Day 4 - 480mg (4 x 120mg capsules) once daily with high fat meal, Day 7 - 480mg (4 x 120mg capsules) once daily fasted, and Day 10 - 480mg (4 x 120mg capsules) once daily with low fat meal. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TP 3654 | Drug | TP 3654 is an investigational orally delivered drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Part A - The maximum concentration (Cmax) of TP-3654 in a capsule formulation | 2 weeks | |
| Part A - The area under the curve (AUC) of TP-3654 in a capsule formulation | 2 weeks | |
| Part A - Ratio of Peak Plasma Concentration (Cmax) of TP-3654 tablet versus TP-3654 capsule under fasted conditions | 2 weeks | |
| Part B - The maximum concentration (Cmax) of TP-3654 in a tablet formulation | 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with Treatment Emergent Adverse Events (TEAE) | TEAEs will be monitored from first dose to 30 days after the last dose | 6 weeks |
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Inclusion Criteria:
Participant has provided written informed consent.
Participant is ≥ 18 to ≤ 65 years of age.
Participant is willing and able to consume the prescribed standard meals.
Participant agrees to use an acceptable method of contraception as described in Section 8.5.4 for the duration of the study and agrees to continue use for 3 months after the final dose (male participants) or for 6 months after the final dose (female participants).
Male participant agrees not to donate sperm during the study and for 3 months after the last dose of study drug. Female participant agrees not to donate eggs for the duration of the study and for 6 months after the last dose of study drug.
Participant has a BMI ≥ 18.5 and ≤ 32 kg/m2 at screening.
Participant is generally healthy, as determined by the Investigator based on medical history, physical examination, clinical laboratory test results, vital signs, and 12-lead electrocardiogram (ECG) at screening. In particular:
Participant agrees to avoid the use of concomitant medications (except hormonal contraception or medication provided by the site staff under the direction of the Investigator) from screening through the final follow-up visit.
Participant agrees to abstain from alcohol, recreational drugs (including marijuana), and nicotine from screening through the final follow-up visit.
Participant is willing and able to remain confined in the Clinical Research Unit for the duration of the inpatient period (13 days for Part A or 10 days for Part B)
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Frontage Investigative Site | Secaucus | New Jersey | 07094 | United States |
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| ID | Term |
|---|---|
| C117473 | TP 3654 |
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| Part A - Sequence 4 | Experimental | Following a screening period of up to 28 days, eligible participants will be admitted to the clinical research unit on Day -1. Participants will fast overnight from Day -1 to Day 1. On Day 1, participants randomly assigned to Sequence 4 will take TP 3654 with or without food as follows: Day 1 - 480mg (4 x 120mg capsules) once daily with high fat meal, Day 4 - 480mg (4 x 120mg capsules) once daily with low fat meal, Day 7 - 480mg (2 x 240mg tablets) once daily fasted, and Day 10 - 480mg (4 x 120mg capsules) once daily fasted. |
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| Part B - Sequence 1 | Experimental | Following a screening period of up to 28 days, eligible participants will be admitted to the clinical research unit on Day -1. Participants will fast overnight from Day -1 to Day 1. On Day 1, participants randomly assigned to Sequence 1 will take TP 3654 tablets with or without food as follows: Day 1 - 480mg once daily with low fat meal, Day 4 - 480mg once daily fasted, and Day 7 - 480mg once daily with high fat meal. |
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| Part B - Sequence 2 | Experimental | Following a screening period of up to 28 days, eligible participants will be admitted to the clinical research unit on Day -1. Participants will fast overnight from Day -1 to Day 1. On Day 1, participants randomly assigned to Sequence 2 will take TP 3654 tablets with or without food as follows: Day 1 - 480mg once daily fasted, Day 4 - 480mg once daily with high fat meal, and Day 7 - 480mg once daily with low fat meal. |
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| Part B - Sequence 3 | Experimental | Following a screening period of up to 28 days, eligible participants will be admitted to the clinical research unit on Day -1. Participants will fast overnight from Day -1 to Day 1. On Day 1, participants randomly assigned to Sequence 3 will take TP 3654 tablets with or without food as follows: Day 1 - 480mg once daily with high fat meal, Day 4 - 480mg once daily with low fat meal, and Day 7 - 480mg once daily fasted. |
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