TD-3504 SAD in Healthy Subjects and Subjects With Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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This study is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single-dose TD-3504 and single dose 15N2-tofacitinib in healthy subjects and subjects with UC. The relative bioavailability of tofacitinib released from TD-3504 compared to co-administered oral heavy-labeled tofacitinib (15N2-tofacitinib) will also be evaluated.

Official Title
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Study 0146: A Phase 1a, Double-Blinded, Randomized, Placebo Controlled, Single Ascending Dose (SAD) Study to Evaluate the Safety, Tolerability, and Systemic Exposure of TD-3504 in Healthy Subjects and Subjects With Ulcerative Colitis (UC)

Conditions
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Active Mild Ulcerative Colitis, Active Moderate Ulcerative Colitis, Healthy Subjects

Intervention / Treatment
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* Drug: TD-3504
* Drug: 15N2-tofacitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 18 to 55 years old Male subjects must abstain from sexual intercourse or use a highly effective method of birth control Women of child bearing potential must have a negative pregnancy test and either abstain from sex or use a highly effective method of birth control Body Mass Index (BMI) 18 to 32 kg/m2 Willing and able to give informed consent Additional inclusion criteria apply Inclusion Criteria for Ulcerative Colitis (UC) subjects: Subject has a history of UC Subject is either not taking any medication for UC or has been taking a stable dose of ulcerative colitis medications for ≥ 14 days Additional inclusion criteria apply Exclusion Criteria: Is positive for hepatitis A, B or C, HIV or tuberculosis Has clinically significant abnormalities in baseline laboratory evaluations Subject has a clinically significant abnormal electrocardiogram (ECG) Participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to screening (or within 60 days prior to screening if investigational drug was a biologic, or is currently participating in another trial of an investigational drug (or medical device) Additional exclusion criteria apply Exclusion Criteria for Healthy Subjects: Use of prescription drugs or any chronic over the counter medications within 14 days prior to clinic admission or requires continuing use during study participation, with the exception of hormonal contraceptives or hormone replacement therapy or standard daily multivitamin. Additional exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TD-3504 Low-Dose<br>6 healthy subjects and 6 ulcerative colitis subjects will be randomized to receive low-dose TD-3504 and low-dose of 15N2-tofacitinib orally single dose. | Drug: TD-3504<br>* TD-3504<br>Drug: 15N2-tofacitinib<br>* 15N2-tofacitinib<br>|
| Experimental: TD-3504 Mid-Dose<br>6 healthy subjects will be randomized to receive mid-dose TD-3504 and low-dose of 15N2-tofacitinib orally single dose. | Drug: TD-3504<br>* TD-3504<br>Drug: 15N2-tofacitinib<br>* 15N2-tofacitinib<br>|
| Experimental: TD-3504 High-Dose<br>6 healthy subjects will be randomized to receive high-dose TD-3504 and low-dose of 15N2-tofacitinib orally single dose. | Drug: TD-3504<br>* TD-3504<br>Drug: 15N2-tofacitinib<br>* 15N2-tofacitinib<br>|
| Placebo Comparator: Placebo<br>6 healthy subjects and 2 ulcerative colitis subjects to receive placebo orally single dose. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety & tolerability of TD-3504 by assessing the number, severity, and type of adverse events | To assess the safety & tolerability of TD-3504 following single escalating doses of TD-3504 co-administered with a low dose of 15N2 tofacitinib for 8 days in healthy subjects and subjects with UC by assessing the number, severity, and type of treatment related adverse events. | Day 1 through Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety & tolerability of TD-3504 by assessing treatment related changes safety laboratory values | To assess the safety & tolerability of TD-3504 following single escalating doses of TD-3504 co-administered with a low dose of 15N2 tofacitinib for 8 days in healthy subjects and subjects with UC by assessing treatment related changes safety laboratory values. | Day 1 through Day 8 | 
| Systemic area under the curve of TD-3504 | To assess the systemic exposure of TD-3504 following single escalating doses of TD-3504 and co-administered 15N2-tofacitinib. | Day 1 through Day 4 | 
| Systemic Cmax of TD-3504 | To assess the systemic exposure of TD-3504 following single escalating doses of TD-3504 and co-administered 15N2-tofacitinib. | Day 1 | 
| Systemic area under the curve of tofacitinib | To assess the systemic exposure of tofacitinib following single escalating doses of TD-3504 and co-administered 15N2-tofacitinib. | Day 1 through Day 4 | 
| Systemic Cmax of tofacitinib | To assess the systemic exposure of tofacitinib following single escalating doses of TD-3504 and co-administered 15N2-tofacitinib. | Day 1 | 
| Systemic area under the curve of 15N2-tofacitinib | To assess the systemic exposure of following single escalating doses of TD-3504 and co-administered 15N2-tofacitinib. | Day 1 through Day 4 | 
| Systemic Cmax of 15N2-tofacitinib | To assess the systemic exposure of following single escalating doses of TD-3504 and co-administered 15N2-tofacitinib. | Day 1 | 
| Tofacitinib relative bioavailability by area under the curve comparison | To assess the relative bioavailability of tofacitinib from TD-3504 relative to 15N2-tofacitinib. | Day 1 through Day 4 | 
| Tofacitinib relative bioavailability by Cmax comparison | To assess the relative bioavailability of tofacitinib from TD-3504 relative to 15N2-tofacitinib. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Active Mild Ulcerative Colitis, Active Moderate Ulcerative Colitis, Healthy Subjects