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

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 and inhaled 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.

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.