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

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)

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.

Study Overview

• Status: Completed
• Conditions: Active Mild Ulcerative Colitis, Active Moderate Ulcerative Colitis, Healthy Subjects
• Intervention / Treatment: Drug: Placebo; Drug: TD-3504; Drug: 15N2-tofacitinib

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 4, 2017
• Primary Completion (ACTUAL): November 8, 2017
• Study Completion (ACTUAL): November 8, 2017

Study Registration Dates

• First Submitted: March 24, 2017
• First Submitted That Met QC Criteria: March 31, 2017
• First Posted (ACTUAL): April 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Active Mild Ulcerative Colitis, Active Moderate Ulcerative Colitis, Healthy Subjects
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: 0146 (SDSU IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No