SAD and MAD Study to Evaluate Safety, Tolerability, and Pharmacokinetics (PK) of TD-1473 in Healthy Subjects

A Double-blinded, Randomized, Placebo-controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TD-1473 in Healthy Subjects

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of single ascending doses and multiple ascending doses of the investigational drug TD-1473 compared to placebo in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: TD-1473 for SAD; Drug: Placebo for SAD; Drug: TD-1473 for MAD; Drug: Placebo for MAD

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or female 19 to 55 years old
• Willing and able to give informed consent
• Body Mass Index (BMI) 18 to 30 kg/m2
• 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
• Additional inclusion criteria apply

Exclusion Criteria:

• Positive for hepatitis A, B, or C, HIV, or tuberculosis (TB)
• Clinically significant abnormalities in baseline results of laboratory evaluations
• Evidence or history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of dosing), hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease
• 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)
• 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.
• Additional exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TD-1473 for SAD; 6 of out 8 subjects per cohort will be randomized to receive TD-1473	Drug: TD-1473 for SAD; SAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (up to 5 dose ascending cohorts) to receive either TD-1473 or placebo. The study drug (TD-1473 or placebo) will be administered orally as a single dose.
Placebo Comparator: Placebo for SAD; 2 of out 8 subjects per cohort will be randomized to receive placebo	Drug: Placebo for SAD; SAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (up to 5 dose ascending cohorts) to receive either TD-1473 or placebo. The study drug (TD-1473 or placebo) will be administered orally as a single dose.
Experimental: TD-1473 for MAD; 6 of out 8 subjects per cohort will be randomized to receive TD-1473	Drug: TD-1473 for MAD; MAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (up to 4 cohorts) to receive either TD-1473 or placebo. The study drug (TD-1473 or placebo) will be administered orally for a total of 14 days of dosing.
Placebo Comparator: Placebo for MAD; 2 of out 8 subjects per cohort will be randomized to receive placebo	Drug: Placebo for MAD; MAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (up to 4 cohorts) to receive either TD-1473 or placebo. The study drug (TD-1473 or placebo) will be administered orally for a total of 14 days of dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and tolerability of SAD and MAD of TD-1473 in healthy subjects by assessing the number, severity and type of adverse events, including changes in vital signs, physical examinations, laboratory safety tests and ECGs	Day 1 through Day 8 (SAD) or 21 (MAD)

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under curve (AUC) in plasma, urine and feces	Day 1 through Day 4-6 (SAD)
Cmax in plasma, urine and feces	Day 1 through Day 4-6 (SAD)
Tmax in plasma, urine and feces	Day 1 through Day 4-6 (SAD)
Terminal elimination half-life (t1/2) in plasma, urine and feces	Day 1 through Day 4-6 (SAD)
Amount excreted in urine (Aeu)	Day 1 through Day 4-6 (SAD)
Amount excreted in feces (Aef)	Day 1 through Day 4-6 (SAD)
AUC in plasma, urine and feces	Day 1 through Day 17-19 (MAD)
Cmax in plasma, urine and feces	Day 1 through Day 17-19 (MAD)
Tmax in plasma, urine and feces	Day 1 through Day 17-19 (MAD)
t1/2 in plasma, urine and feces	Day 1 through Day 17-19 (MAD)
Aeu	Day 1 through Day 17-19 (MAD)
Aef	Day 1 through Day 17-19 (MAD)

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Publications and helpful links

General Publications

• Sandborn WJ, Nguyen DD, Beattie DT, Brassil P, Krey W, Woo J, Situ E, Sana R, Sandvik E, Pulido-Rios MT, Bhandari R, Leighton JA, Ganeshappa R, Boyle DL, Abhyankar B, Kleinschek MA, Graham RA, Panes J. Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme. J Crohns Colitis. 2020 Sep 16;14(9):1202-1213. doi: 10.1093/ecco-jcc/jjaa049.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: January 13, 2016
• First Posted (Estimate): January 15, 2016

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: volunteers; Phase 1; SAD; multiple ascending dose; MAD; first-in-human; Single ascending dose; TD-1473
• Other Study ID Numbers: 0140

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.