Induction, STabilization, Adherence and Retention Trial (ISTART) of OX219 Buprenorphine/Naloxone

This is a prospective, randomized, multicenter, parallel-group, active-controlled
non-inferiority study comparing treatment efficacy and adherence of the sublingual (SL)
tablets of OX219 versus SUBOXONE Film during the first 15 days of treatment and to explore
switching between OX219 and SUBOXONE Film treatments.

Approximately 787 opioid-dependent adult subjects will be screened.

Total study treatment 36 days (screening 1-7 days) , number of visits 9-10.

Inclusion Criteria:

1. Male/female 18 - 65 years old

2. Able to read, comprehend & sign the informed consent form

3. Meet opioid dependence criteria in DSM-IV-TR the past 12 months

4. Have a Buprenorphine-negative UDS &/or urine dipstick

5. Prepared to abstain from opioids other than the study drug & from other addictive
drugs

6. Negative urine pregnancy test

7. Females of childbearing potential who use a reliable method of contraception. Females
of non-childbearing potential; surgically sterile or post-menopausal as defined by
being at least 50 years of age & having an absence of menses for at least 2 years

8. Clearance from the prescribing MD to be withdrawn from their prescribed opioids for
subjects receiving opioids for pain

9. Lack of clinically significant abnormalities in health assessments performed at
screening. Unclear cases should be approved by the medical monitor

10. At leastmild withdrawal symptoms (COWS ≥ 9)

Exclusion Criteria:

1. Pregnant, lactating or planning to be pregnant during study

2. Unwilling/unable to comply with the requirements of the protocol (e.g., pending
incarceration) are in a situation/condition that may interfere with participation in
the study

3. Prescribed treatment with generic buprenorphine monotherapy within 90 days prior
start of treatment

4. Daily dose of methadone over 30 mg during the past week or who received the last dose
of methadone less than 30 hours prior to treatment

5. Participating in other clinical studies in which medications is delivered or who have
used an investigational drug/device within the last 30 days

6. Allergy, sensitivity or intolerance to BUP, NAL or any related drug; history of drug
hypersensitivity or intolerance which, in the opinion of the investigator, would
compromise the safety of the subject/study

7. Staff, affiliated with, or family member of the staff directly involved with this
study

8. Serious untreated Axis I DSM-IV-TR psychiatric comorbidity (actively suicidal or
homicidal, have untreated schizophrenia)

9. Tongue/oral deformities that may affect the absorption of the drug products

10. Current/history of clinically significant medical disorder or condition which would
jeopardize the safety or impact the validity of the results. Unclear cases should be
discussed with & approved by the medical monitor

11. HIV-seropositive with a CD4+ count < 200, active AIDS defining infection in the last
120 days

12. Have Class III/IV congestive heart failure, symptomatic myocardial ischemia or
history of long QT syndrome (or an immediate family member with this condition)

13. Currently taking Class 1A antiarrhythmic medications (e.g., quinidine, procainamide,
& disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, &
dofetilide)

14. Have uncontrolled hypertension, pulse oximetry ≤ 92%or clinically significant
abnormality on 12-lead ECG, including a corrected QT (QTc) interval > 450 ms

15. Severe liver disease