Lofexidine ADME & Mass Balance in Volunteers

Inclusion Criteria:

- Subject must be a male or non-pregnant, non-breastfeeding female.

- Subject must be between 18 and 50 years of age (inclusive).

- Subject's Body Mass Index (BMI) must be between 18 and 30 kg/m2 (inclusive), and
subject must weigh a minimum of 50 kg (110 lbs).

- Female subjects must agree to use one of the following forms of birth control from
screening until 14 days after completion of the study:

- Vasectomized partner (at least 6 months prior to dosing)

- Post-menopausal (at least 2 years prior to dosing)

- Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) at
least 6 months prior to dosing

- Double barrier (diaphragm with spermicide; condoms with spermicide)

- IUD (intra-uterine device)

- Abstinence (must agree to use a double barrier method if they become sexually active
during the study)

- Implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive
months prior to study dosing and throughout the study duration

- Oral, patch, and injected contraceptives or vaginal hormonal device (i.e. NuvaRing®)
in use for at least 3 consecutive months prior to study dosing and throughout the
study duration.

- Subject must voluntarily consent to participate in this study and provide their
written informed consent prior to start of any study- specific procedures.

- Subject is willing and able to remain in the study unit for the entire duration of
each confinement period.

- Subject's vital signs must be within the following ranges to be included: Vital signs
measured sitting after 3 minutes rest; heart rate: 50-90 bpm; systolic BP: 100-140
mmHg; diastolic BP: 50-90 mmHg, and oral temperature within the normal range of
35.6-37.7° C. Out-of-range vital signs may be repeated once. Predose vital signs will
be assessed by the Principal Investigator or designee (e.g., a medically qualified
sub-investigator) prior to study drug administration. The Principal Investigator or
designee will verify the eligibility of each subject with out-of-range vital signs and
document approval prior to dosing.

- For the study period in which the subject is assigned to receive Treatment A
(lofexidine oral solution containing 14C-lofexidine), subject must be:

- Willing to eat entire meals and snacks provided during confinement at the research
facility; and understand that the diet will include foods with high fiber content and
possibly prune juice.

- Willing to remain in the clinical research center for a minimum of 7 consecutive days
during pre-dose, dose, and post-dose evaluation periods. Subjects must be willing to
stay for an additional 24 to 48 hours if necessary.

- Willing to collect all urine and fecal samples for the duration of the study period as
required.

Exclusion Criteria:

- History or presence of clinically significant cardiovascular, pulmonary, hepatic,
renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,
neurologic, oncologic, or psychiatric disease or any other condition that, in the
opinion of the Investigator, would jeopardize the safety of the subject or the
validity of the study results.

- Has a clinically significant abnormal finding on the physical exam, medical history,
ECG, or clinical laboratory results at screening.

- History of any syncopal episode or seizures.

- Presence of acute disease state (eg, nausea, vomiting, fever, diarrhea) within 7 days
prior to scheduled dose administration.

- History or presence of allergic or adverse response to lofexidine or related drugs.

- Has been on a significantly abnormal diet during the 4 weeks preceding the first dose
of study medication.

- Has donated blood or plasma within 30 days prior to the first dose of study
medication.

- Has participated in a radiolabeled clinical trial within the last 12 months prior to
the first dose of study medication.

- Has participated in another clinical trial (randomized subjects only) within 30 days
prior to the first dose of study medication.

- Has used any over-the-counter (OTC) medication, including nutritional supplements,
within 7 days prior to the first dose of study medication.

- Has used any prescription medication, except hormonal contraceptive or hormonal
replacement therapy, within 14 days prior to the first dose of study medication.

- Subjects that have discontinued the use of implanted, intrauterine, or injected
hormonal contraceptives must not have used any for 6 months prior to study start.

- Subjects that have discontinued the use of oral, patch, or vaginal hormonal
contraceptives must not have used any for 1 month prior to study start.

- Has been treated with any known drugs that are moderate or strong inhibitors/inducers
of CYP enzymes such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc.,
within 30 days prior to the first dose of study medication and that in the
Investigator's judgment may impact subject safety or the validity of the study
results.

- Has smoked or used tobacco products within 60 days prior to the first dose of study
medication.

- Has any prior history of substance abuse or treatment (including alcohol) within the
past 2 years.

- Is a female with a positive pregnancy test result.

- Has a positive urine screen for drugs of abuse (amphetamines, barbiturates,
benzodiazepines, cocaine, cannabinoids, opiates).

- Has had a positive test for, or has been treated for hepatitis B, hepatitis C, or
Human Immunodeficiency Virus (HIV).

- Has orthostatic hypotension at screening defined as a drop in systolic blood pressure
≥ 20 mmHg or a fall in diastolic blood pressure ≥ 10 mmHg following a 2 minute stand.
Out-of-range vital signs may be repeated once. Predose vital signs will be assessed by
the Principal Investigator or designee (e.g., a medically qualified sub-investigator)
prior to study drug administration. The Principal Investigator or designee will verify
the eligibility of each subject with out-of-range vital signs and document approval
prior to dosing.

- Subjects with a QTcB greater than 450 msec (males) or greater than 470 msec (females),
at screening obtained after 5 minutes rest in a supine position using the ECG machine
algorithm.

- Has irregular bowel habits. ("Irregular" being defined for the purpose of this study
as NOT having a bowel movement at least every 2 days.)

- Has been exposed to radiation, including dental or medical imaging such as x ray or
tomography, in the 6 months prior to dose administration.