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

Primary Purpose

Chronic Obstructive Pulmonary Disease (COPD)

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

TD-4208

About this trial

This is an interventional basic science trial for Chronic Obstructive Pulmonary Disease (COPD) focused on measuring COPD, ADME, Healthy Normal Males, Phase 1

Eligibility Criteria

19 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

Subject has a body mass index 19 to 32 kg/m2, inclusive, and weigh at least 55 kg.
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.
Subject is negative for hepatitis B, hepatitis C, and HIV antibodies.
Subject has no clinically relevant abnormalities as determined by the investigator in the results of Screening or Day -1 laboratory evaluations.

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 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).
Subject has a known hypersensitivity towards medications similar to TD-4208 or excipients contained in TD-4208.
Subject has previously participated in a trial for TD-4208.
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 (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.
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.
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.

Sites / Locations

Celerion

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Study Population

Arm Description

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.

Outcomes

Primary Outcome Measures

[14C] total radioactivity in urine and reported as the recovery in urine as a percentage of the administered dose

[14C] total radioactivity in feces and reported as the recovery in feces as a percentage of the administered dose

Secondary Outcome Measures

Whole blood concentrations of total radioactivity

Plasma concentrations of total radioactivity

Plasma concentrations of TD-4208

Plasma concentrations of THRX-195518

Full Information

NCT ID

NCT02772159

First Posted

June 10, 2015

Last Updated

February 22, 2022

Sponsor

Mylan Inc.

Collaborators

Theravance Biopharma

1. Study Identification

Unique Protocol Identification Number

NCT02772159

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

June 2015 (undefined)

Primary Completion Date

April 2016 (Actual)

Study Completion Date

April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mylan Inc.

Collaborators

Theravance Biopharma

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD, ADME, Healthy Normal Males, Phase 1

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Study Population

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

TD-4208

Other Intervention Name(s)

revefenacin

Intervention Description

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.

Primary Outcome Measure Information:

Title

[14C] total radioactivity in urine and reported as the recovery in urine as a percentage of the administered dose

Time Frame

up to 336 hours

Title

[14C] total radioactivity in feces and reported as the recovery in feces as a percentage of the administered dose

Time Frame

up to 336 hours

Secondary Outcome Measure Information:

Title

Whole blood concentrations of total radioactivity

Time Frame

up to 336 hours

Title

Plasma concentrations of total radioactivity

Time Frame

up to 336 hours

Title

Plasma concentrations of TD-4208

Time Frame

up to 336 hours

Title

Plasma concentrations of THRX-195518

Time Frame

up to 336 hours

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

19 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject has a body mass index 19 to 32 kg/m2, inclusive, and weigh at least 55 kg. 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. Subject is negative for hepatitis B, hepatitis C, and HIV antibodies. Subject has no clinically relevant abnormalities as determined by the investigator in the results of Screening or Day -1 laboratory evaluations. 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 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). Subject has a known hypersensitivity towards medications similar to TD-4208 or excipients contained in TD-4208. Subject has previously participated in a trial for TD-4208. 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 (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. 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Monitor

Organizational Affiliation

Theravance Biopharma, US, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Celerion

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68502

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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

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