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

• ClinicalTrials.gov Identifier: NCT03408470
• Recruitment Status: Completed
• First Posted: January 24, 2018
• Last Update Posted: January 14, 2021
• Sponsor: Theravance Biopharma
• Information provided by (Responsible Party): Theravance Biopharma

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Intestinal Disorders; Bowel Diseases, Inflammatory	Drug: TD-1473 oral capsule; Drug: [14C]-TD-1473 IV bolus; Drug: [14C]-TD-1473 Oral Capsule	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: January 31, 2018
• Actual Primary Completion Date: February 21, 2018
• Actual Study Completion Date: February 21, 2018

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Maximum observed concentration (Cmax) in Plasma [ Time Frame: Up to 15 days ]
2. Time to maximum observed concentration (tmax) in Plasma [ Time Frame: Up to 15 days ]
3. Area under the concentration-time curve from hour 0 to the last measurable concentration (AUC0-last) in Plasma [ Time Frame: Up to 15 days ]
4. Area under the concentration-time curve extrapolated to infinity (AUC0-inf) in Plasma [ Time Frame: Up to 15 days ]
5. Apparent terminal elimination half-life (t1/2) in Plasma [ Time Frame: Up to 15 days ]
6. Apparent clearance (Cl/F) in Plasma [ Time Frame: Up to 15 days ]
7. Apparent volume of distribution (Vz/F) in Plasma [ Time Frame: Up to 15 days ]
8. Absolute bioavailability (%F) in Plasma [ Time Frame: Up to 15 days ]

Secondary Outcome Measures :

1. Amount excreted in urine (Aeu) over the sampling interval in Urine [ Time Frame: Up to 15 days ]
2. Renal clearance (CLr) in Urine [ Time Frame: Up to 15 days ]
3. The percent excreted in urine (%Feu) in Urine [ Time Frame: Up to 15 days ]
4. Amount excreted in feces (Aef) over the sampling interval in Feces [ Time Frame: Up to 15 days ]
5. The percent excreted in feces (%Fef) [ Time Frame: Up to 15 days ]

Other Outcome Measures:

1. Metabolites in Plasma [ Time Frame: Up to 15 days ]
   TD 1473 metabolite profiling will be performed in plasma containing sufficient amounts of radioactivity
2. Metabolites in Urine [ Time Frame: Up to 15 days ]
   TD 1473 metabolite profiling will be performed in urine containing sufficient amounts of radioactivity
3. Metabolites in Feces [ Time Frame: Up to 15 days ]
   TD-1473 metabolite profiling will be performed in feces containing sufficient amounts of radioactivity

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Males only
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Nebraska

Celerion

Lincoln, Nebraska, United States, 68502

Sponsors and Collaborators

Theravance Biopharma

Investigators

• Study Director: Medical Monitor; Theravance Biopharma

More Information

• Responsible Party: Theravance Biopharma
• ClinicalTrials.gov Identifier: NCT03408470
• Other Study ID Numbers: 0152
• First Posted: January 24, 2018
• Last Update Posted: January 14, 2021
• Last Verified: January 2021

Individual Participant Data (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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Theravance Biopharma:

Absolute Bioavailability; ADME; Healthy Normal Males

Additional relevant MeSH terms:

Intestinal Diseases; Inflammatory Bowel Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis