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

• ClinicalTrials.gov Identifier: NCT02657122
• Recruitment Status: Completed
• First Posted: January 15, 2016
• Last Update Posted: January 19, 2021
• Sponsor: Theravance Biopharma
• Information provided by (Responsible Party): Theravance Biopharma

Tracking Information

• First Submitted Date: November 25, 2015
• First Posted Date: January 15, 2016
• Last Update Posted Date: January 19, 2021
• Actual Study Start Date: December 2015
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 13, 2016): 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 [ Time Frame: Day 1 through Day 8 (SAD) or 21 (MAD) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 13, 2016)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: SAD and MAD Study to Evaluate Safety, Tolerability, and Pharmacokinetics (PK) of TD-1473 in Healthy Subjects
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Healthy

Intervention

• 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.
• 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.
• 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.
• 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.

Study Arms

• Experimental: TD-1473 for SAD
  6 of out 8 subjects per cohort will be randomized to receive TD-1473
  Intervention: Drug: TD-1473 for SAD
• Placebo Comparator: Placebo for SAD
  2 of out 8 subjects per cohort will be randomized to receive placebo
  Intervention: Drug: Placebo for SAD
• Experimental: TD-1473 for MAD
  6 of out 8 subjects per cohort will be randomized to receive TD-1473
  Intervention: Drug: TD-1473 for MAD
• Placebo Comparator: Placebo for MAD
  2 of out 8 subjects per cohort will be randomized to receive placebo
  Intervention: Drug: Placebo for MAD

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 13, 2016): 72
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 19 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02657122
• Other Study ID Numbers: 0140
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

• Current Responsible Party: Theravance Biopharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Theravance Biopharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor; Theravance Biopharma

• PRS Account: Theravance Biopharma
• Verification Date: January 2021