TD-1473 Absorption, Distribution, Metabolism and Excretion (ADME) Study in Healthy Male Subjects

A 2-Cohort Study to Evaluate the Absolute Bioavailability, Absorption, Distribution, Metabolism and Excretion of TD-1473 Following an Intravenous and an Oral Dose of [14C]-TD-1473 in Healthy Male Subjects

This is an open-label, 2-cohort study to evaluate the absolute bioavailability, absorption, distribution, metabolism and excretion of TD-1473 in healthy male subjects. Subjects in cohort 1 will receive a single oral dose of TD-1473 and a single intravenous bolus dose of [14C]-TD-1473. Subjects in cohort 2 will receive a single oral dose of [14C]-TD-1473 only.

Study Overview

• Status: Completed
• Conditions: Bowel Diseases, Inflammatory; Intestinal Disorders
• Intervention / Treatment: Drug: TD-1473 oral capsule; Drug: [14C]-TD-1473 IV bolus; Drug: [14C]-TD-1473 Oral Capsule

• Study Type: Interventional
• Enrollment (Actual): 20
• 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: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subject is a healthy, nonsmoking male, 19 to 55 years old, inclusive
• Subject has a body mass index (BMI) 19 to 32 kg/m2, inclusive, and weighs at least 50 kg
• Subject is healthy as determined by the PI or designee based on medical history and physical examination performed at Screening and Day -1
• Additional inclusion criteria apply

Exclusion Criteria:

• Subject has any condition possibly affecting drug absorption (e.g., previous surgery on the gastrointestinal tract [including removal of parts of the stomach, bowel, liver, gall bladder, or pancreas])
• Subject has a known hypersensitivity towards medications similar to TD 1473 or excipients contained in TD 1473
• Subject regularly works with ionizing radiation or radioactive material
• Subject has been exposed to ionizing radiations, within 1 year prior to the start of the study, as external irradiation (i.e., radiological examination including CT scan, excluding dental radiography) or internal radiation (i.e., diagnostic nuclear medicine procedure) or have participated in a radiolabeled study in the last 12 months
• Subject, who, for any reason, is deemed by the PI or designee or Sponsor to be inappropriate for this study or have any condition which would confound or interfere with the evaluation of the safety, tolerability, and PK of the investigational drug or prevent compliance with the study protocol
• Additional exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TD-1473 Oral Capsule & [14C]-TD-1473 IV bolus; Cohort 1 - One oral dose and IV bolus administered 1 hr after oral dose of TD-1473	Drug: TD-1473 oral capsule; (Intervention description included in arm description); Drug: [14C]-TD-1473 IV bolus; (Intervention description included in arm description)
Experimental: [14C]-TD-1473 Oral Capsule; Cohort 2 - One oral dose	Drug: [14C]-TD-1473 Oral Capsule; (Intervention description included in arm description)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration (Cmax) in Plasma	Up to 15 days
Time to maximum observed concentration (tmax) in Plasma	Up to 15 days
Area under the concentration-time curve from hour 0 to the last measurable concentration (AUC0-last) in Plasma	Up to 15 days
Area under the concentration-time curve extrapolated to infinity (AUC0-inf) in Plasma	Up to 15 days
Apparent terminal elimination half-life (t1/2) in Plasma	Up to 15 days
Apparent clearance (Cl/F) in Plasma	Up to 15 days
Apparent volume of distribution (Vz/F) in Plasma	Up to 15 days
Absolute bioavailability (%F) in Plasma	Up to 15 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Amount excreted in urine (Aeu) over the sampling interval in Urine	Up to 15 days
Renal clearance (CLr) in Urine	Up to 15 days
The percent excreted in urine (%Feu) in Urine	Up to 15 days
Amount excreted in feces (Aef) over the sampling interval in Feces	Up to 15 days
The percent excreted in feces (%Fef)	Up to 15 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolites in Plasma	TD 1473 metabolite profiling will be performed in plasma containing sufficient amounts of radioactivity	Up to 15 days
Metabolites in Urine	TD 1473 metabolite profiling will be performed in urine containing sufficient amounts of radioactivity	Up to 15 days
Metabolites in Feces	TD-1473 metabolite profiling will be performed in feces containing sufficient amounts of radioactivity	Up to 15 days

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2018
• Primary Completion (Actual): February 21, 2018
• Study Completion (Actual): February 21, 2018

Study Registration Dates

• First Submitted: January 12, 2018
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (Actual): January 24, 2018

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: ADME; Absolute Bioavailability; Healthy Normal Males
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: 0152

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