TD-4208 Absorption, Distribution, Metabolism and Excretion (ADME) Study in Healthy Male Subjects

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

Official title:

A Single-Dose, Fixed-Sequence, Two-Period Study to Evaluate the Absorption, Distribution, Metabolism, Excretion of TD-4208 Following an IV Infusion and an Oral Dose of [14C]-Labeled TD-4208 in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02772159
• Other study ID #: 0130
• Status: Completed
• Phase: Phase 1
• Start date: June 2015
• Est. completion date: April 2016

Study information

• Verified date: February 2022
• Source: Viatris Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the absorption, distribution, metabolism and excretion of an investigational medication used to treat chronic obstructive pulmonary disease (COPD). The study drug will be tested in 6 healthy normal males. Dosing will include a single dose of study drug administered via an IV Infusion and an Oral Dose. There will be a 28 day washout period between each of the 2 dosing routes.

Description:

This is an open-label, fixed-sequence, two-period study in up to 12 healthy male subjects. The present study is designed to fully characterize the rates and routes of elimination of TD 4208 using radiolabeled drug administered via the oral and IV route. This study will provide information regarding the metabolic fate of TD 4208, the need for evaluation of potential drug-drug interactions, the need for studies in special populations and the absolute oral bioavailability of TD-4208. The results from this study will allow a comprehensive comparison between animal and human routes of elimination and metabolic profiles of TD 4208.

This study will be conducted in a small number of healthy male subjects (up to n=12) to minimize the number of individuals exposed to radioactivity. Each subject will receive the following treatments: Treatment A (Period 1): 20 μg IV infusion of [14C] TD-4208 administered in a fasted state over 30 minutes. Treatment B (Period 2): 200 μg oral solution of [14C] TD-4208 administered in a fasted state. Blood, urine, feces, and vomitus (if applicable) will be collected until the subject is released during Periods 1 and 2. In Periods 1 and 2, subjects may remain in the clinical research unit for a maximum of 15 days. Between the dosing in periods 1 and 2, there will be washout intervals of at least 28 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 19 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Subject has a body mass index 19 to 32 kg/m2, inclusive, and weigh at least 55 kg.

2. Subject has normal blood pressure (BP) and heart rate (HR), measured after resting seated or supine for approximately 5 minutes. Normal BP is defined as 90 to 140 mm Hg systolic and 50 to 90 mm Hg diastolic. Normal HR is defined as 40 to 99 beats per minute.

3. Subject is negative for hepatitis B, hepatitis C, and HIV antibodies.

4. Subject has no clinically relevant abnormalities as determined by the investigator in the results of Screening or Day -1 laboratory evaluations.

Exclusion Criteria:

1. 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]).

2. Subject has participated in another clinical trial of an investigational drug (or medical device) within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to Screening, or are currently participating in another trial of an investigational drug (or medical device).

3. Subject has a known hypersensitivity towards medications similar to TD-4208 or excipients contained in TD-4208.

4. Subject has previously participated in a trial for TD-4208.

5. Subject regularly works with ionizing radiation or radioactive material.

6. Subject has been exposed to ionizing radiations, within 1 year prior to the start of the study, as external irradiation (radiological examination including CT scan excluding dental radiography) or internal radiation (diagnostic nuclear medicine procedure) or have participated in a radiolabeled study in the last 12 months.

7. Subject has had exposure to external and/or internal radiotherapy with open (i.e., nuclear medicine) and sealed sources (i.e., brachytherapy) within the last 12 months.

8. Subject, who, for any reason, is deemed by the investigator to be inappropriate for this study or have any condition which would confound or interfere with the evaluation of the safety, tolerability, PK of the investigational drug or prevent compliance with the study protocol.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• TD-4208
One dose each of treatments A: [14C] TD-4208 20 µg IV administered in a fasted state over 30 minutes. B: [14C] TD-4208 200 µg oral solution administered in a fasted state.

Locations

Country	Name	City	State
United States	Celerion	Lincoln	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
Mylan Inc.	Theravance Biopharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[14C] total radioactivity in urine and reported as the recovery in urine as a percentage of the administered dose		up to 336 hours
Primary	[14C] total radioactivity in feces and reported as the recovery in feces as a percentage of the administered dose		up to 336 hours
Secondary	Whole blood concentrations of total radioactivity		up to 336 hours
Secondary	Plasma concentrations of total radioactivity		up to 336 hours
Secondary	Plasma concentrations of TD-4208		up to 336 hours
Secondary	Plasma concentrations of THRX-195518		up to 336 hours