Low Dose Naltrexone-buprenorphine Transfer to Vivitrol Injection in Opioid Dependence (BUP/NXT-VIVI)

• ClinicalTrials.gov Identifier: NCT01690546
• Recruitment Status: Completed
• First Posted: September 21, 2012
• Results First Posted: June 1, 2016
• Last Update Posted: June 1, 2016
• Sponsor: Paolo Mannelli
• Collaborator: Alkermes, Inc.
• Information provided by (Responsible Party): Paolo Mannelli, Duke University

Tracking Information

• First Submitted Date: September 19, 2012
• First Posted Date: September 21, 2012
• Results First Submitted Date: February 22, 2016
• Results First Posted Date: June 1, 2016
• Last Update Posted Date: June 1, 2016
• Study Start Date: September 2012
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 25, 2016)

Retention in Treatment [ Time Frame: 4 weeks ]

After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks.

Original Primary Outcome Measures (submitted: September 19, 2012)

Treatment Completion [ Time Frame: 37 days ]

Subjects are required to complete the 9 days of titration for opioid withdrawal. Then the 4 week follow-up period after the Vivitrol injection.

Current Secondary Outcome Measures (submitted: April 25, 2016)

• Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS) [ Time Frame: 4 weeks ]
  After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment. COWS rates eleven common opiate withdrawal signs or symptoms. The summed scores ranged from 0-48, with 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal.
• Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS) [ Time Frame: 4 weeks ]
  After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment. SOWS contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). Total score range is 0 - 64; the higher the score the more withdrawal symptoms.
• Craving [ Time Frame: 4 weeks ]
  Craving, assessed with a 100-point Visual Analog Scale (VAS), ranging from 'not at all' (0) to 'more than ever' (100). The higher the score the higher the craving.
• Illicit Drug Use, Measured by Urine Drug Testing [ Time Frame: 4 weeks ]
  number of participants that tested positive for marijuana, cocaine, and opiates.
• Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire [ Time Frame: Day 9 ]
  Questionnaire consisted of 3 questions.

  1. Were you satisfied with the treatment (range 1-5): Completely satisfied (1) to completely dissatisfied (5).
  2. Were you satisfied with withdrawal treatment (range 1-5): Minimal withdrawal (1) to worse than ever (5).
  3. Did the medication help (range 1-5): Helped a lot (1) to No it did not help (5).

  Lower scores represent greater satisfaction.
• Percentage of Participants Who Adhered to Study Visits. [ Time Frame: baseline to end of study (approximately 40 days) ]
• Percentage of Participants With Adherence to Medication (Naltrexone) [ Time Frame: Day 1 to Day 8 (+/- 2 days) ]
  Participant who took Naltrexone as prescribed.
• Use of Ancillary Medications. [ Time Frame: baseline to week 1 ]
  Number of participants that took ancillary medication
• Number of Participants That Self Reported Illicit Drug Use [ Time Frame: 4 weeks ]
  Participants reported on any illicit drug use to include Cocaine marijuana opiates

Original Secondary Outcome Measures (submitted: September 19, 2012)

Withdrawal Intensity [ Time Frame: 37 days ]

Withdrawal symptoms will be assesssed with the following scales:

• Subjective Opioid Withdrawal Scale (SOWS)
• Clinical Opioid Withdrawal Scale (COWS)
• Craving, assessed with a 20-point Visual Analog Scale (VAS)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Low Dose Naltrexone-buprenorphine Transfer to Vivitrol Injection in Opioid Dependence
• Official Title: An Open Label, Flexible Dose Study of Very Low Doses of Naltrexone-Buprenorphine Transfer to Extend-Release Naltrexone (VIVITROL®) in Opioid Addiction
• Brief Summary: The purpose of this study is to evaluate a very low dose naltrexone-buprenorphine treatment to transfer opioid dependent individuals to extended release naltrexone injection (Vivitrol). The hypothesis is that patients will complete the transfer to Vivitrol successfully, finding the treatment acceptable and showing minimal withdrawal discomfort.

Detailed Description

Thirty-five opioid dependent (OD) volunteers seeking treatment will be enrolled in an open-label, flexible-dosing, outpatient trial at Duke Addictions Program. On days 1-3, participants will receive buprenorphine/naloxone daily at a starting dose of 4mg, progressively decreasing to 2 mg on days 2- 3. Participants will also receive very low dose naltrexone (VLNTX) at a dose of 0.25 mg to 1mg on Days 1-3, 2 to 6 mg on Day 4 and between 10 and 50 mg on Days 5-7. Then a VIVITROL injection, 380 mg, will be administered on Day 8.

Evaluations will occur daily for up to 6 hours until 1 day after VIVITROL injection and then weekly for 4 weeks. Patients will receive ancillary medications as needed and weekly psychosocial intervention. At the end of the study, participants will be offered outpatient treatment of OD at the study site, or will be referred to other treatment programs.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Opiate Dependence

Intervention

• Drug: very low dose naltrexone
  On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
• Drug: extended release naltrexone
  On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
  Other Name: Vivitrol
• Drug: buprenorphine/naloxone
  On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
  Other Name: Suboxone

Study Arms

Experimental: BUP/VLNXT to VIVITROL

On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.

Interventions:

• Drug: very low dose naltrexone
• Drug: extended release naltrexone
• Drug: buprenorphine/naloxone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 25, 2016): 38
• Original Estimated Enrollment (submitted: September 19, 2012): 20
• Actual Study Completion Date: February 2015
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Men and women 18 to 65 years of age who meet DSM-IV criteria for OD of at least six months duration, supported by a positive urine for opiates and a positive naloxone challenge test if the diagnosis is unclear.
2. Individuals must be capable of giving informed consent and capable of complying with study procedures.
3. Participants will be asked to provide locator information including the address and telephone number of a non-drug abusing relative or friend who can reach the participant in emergencies.

Exclusion Criteria:

1. Individuals currently prescribed or regularly taking opiates for chronic pain or medical illness.
2. Individuals regularly using licit or illicit methadone or BUP.
3. Individuals meeting DSM-IV criteria for schizophrenia, schizoaffective or psychotic disorders, or psychiatric disorder (other than substance abuse) requiring intervention.
4. Individuals who are medically unstable, or have liver enzyme function tests greater than two times normal.
5. Individuals with current suicidal risk or 1 or more suicide attempts within the past year.
6. History of accidental drug overdose in the last three years or any other significant history of overdose following detoxification, defined as an episode of opioid-induced unconsciousness or incapacitation.
7. Nursing/pregnant women, or failure in a sexually active man or woman to use adequate contraceptive methods (e.g., oral or depot contraceptives, foam, sponges, and/or condoms)
8. Individuals who are dependent on any other drugs (excluding nicotine)
9. Individuals with known sensitivity to BUP, VIVITROL, NTX, naloxone.
10. Individuals who are court-mandated to treatment.
11. Individuals who have a current or pending legal status, or any other condition that would make them unlikely to be available for the duration of the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01690546
• Other Study ID Numbers: Pro00036909
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Paolo Mannelli, Duke University
• Original Responsible Party: Same as current
• Current Study Sponsor: Paolo Mannelli
• Original Study Sponsor: Same as current
• Collaborators: Alkermes, Inc.

Investigators

• Principal Investigator: Paolo Mannelli, MD; Duke University Health Systems

• PRS Account: Duke University
• Verification Date: April 2016