Clinical trial NCT03656120: A Study of Thienorphine Hydrochloride Tablets in Relapse Prevention Treatment of Opioid Dependence
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase Ⅱb Clinical Trial of Thienorphine Hydrochloride Tablets for the Efficacy, Safety, and Optimal Dosing of Relapse Prevention After Opioid Dependence Detoxification
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Opioid Dependence
Keywords: opioid dependence
thienorphine hydrochloride
Lead sponsor: Central South University
Sponsor class: OTHER
Collaborators: name: Beijing ziduhongye technology development co. LTD
name: Institute of Pharmacology and Toxicology, Academy of Military Medical Science
name: Shanghai Mental Health Center
name: West China Hospital
name: Wuhan Mental Health Centre
First posted: 2018-09-04
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Opioid addiction is common worldwide. Thienorphine hydrochloride is a newly partial opioid receptor agonist drugs. It's affinity with opioid receptors was much higher than opioids, which could effectively prevents opioid dependence by stop opioids competition for opioid receptors and causing opioid dependence. The aim of this research was to determine whether thienorphine hydrochloride would reduce opioid use and better preventing relapse among opioid addicts.

Detailed description: Opioids dependence is a chronic brain disease, with a much higher rate of relapse rate. Relapse prevention is important for opioid dependence treatment. Thienorphine hydrochloride, derivatives of buprenorphine, is one of the receptor partial agonists. Previous research indicated that, it may be a safe and effective treatment for the prevention of opioid dependent patients after detoxification. In this multicenter, randomized, double-blind, placebo-controlled, phase Ⅱb clinical trial, we are aimed to evaluate the efficacy of thienorphine hydrochloride tablets for anti-relapse therapy after opioid dependence detoxification treatment, determining the optimal dose of thienorphine hydrochloride tablets, and further evaluate the safety of thienorphine hydrochloride for patients with opioid dependence. 180 eligible patients are going to be recruited and randomly assigned to 0.2mg/day group, 0.5mg/day group and placebo control group after they provided their consent forms. Subjects in each group would receive assigned treatment for 12 weeks. Primary outcome measure was retention time of each participants during these 12 weeks. Urine test for opioids, changing of withdrawal score and craving, self-reported euphoria after using heroin, subjects and researchers' overall evaluation of treatment efficacy are secondary outcome measures.

Eligibility criteria: Inclusion Criteria:

1. Currently meets the diagnostic criteria for DSM-IV opioid dependence, with a history of opioids using more than 1 year; having relapsed for opioids for at least twice, and meets one of the following criterion:

   1.1 Opioid dependent patients (including heroin dependent patients or patients undergoing methadone maintenance treatment) treated with buprenorphine and meeting the following criteria: 1.1.1 Taking buprenorphine 2 mg per day for at least 3 consecutive days; 1.1.2 Clinical Opioid Withdrawal Symptom Scale (COWS) score ≤ 4; 1.1.3 Negative urine test results for morphine and methadone; 1.2 Having been stopped to using opioids. Negative urine test results for morphine, methadone and buprenorphine. As well as negative result for naloxone-precipitated tests ((including patients returning to the community from drug rehabilitation agencies).
2. Age 18 to 60 years old, male and female
3. Weight 40 \~ 95kg
4. Able to communicate with researchers, willing to receive anti-relapse therapy, and provide signed consent forms.

Exclusion Criteria:

1. Substance dependence other than nicotine;
2. Severe psychiatric disorders;
3. Severe physical illnesses, including severe digestive, cardiovascular, respiratory, and endocrine systems problems;
4. Patients with severe chronic pain;
5. Women in pregnancy or lactation
6. Patients who do not have effective contraception methods
7. Systolic/diastolic pressure is higher than 150/100mmHg or lower than 85/60mmHg
8. Heart rate \<50 beats / min;
9. Severe liver or kidney dysfunction or severe abnormalities confirmed by laboratory test (liver function indicators ALT, AST are more than 3 times higher than the upper limit of normal values; any of the renal function indicators BUN, Cr that is higher than the upper limit of normal 1.5 times and above);
10. Allergic to buprenorphine or other similar drugs;
11. Patients with dysuria or urinary retention symptoms;
12. People with severe habitual constipation;
13. Those with HIV infection;
14. Poor adherence;
15. Participants enrolled in other clinical trials within 4 weeks prior to enrollment.

Primary outcomes:
measure: days of retention in outpatient treatment
timeFrame: up to 12 weeks
Secondary outcomes:
measure: opioids negative rate through urine test
timeFrame: up to 12 weeks
measure: Change of withdrawal score of Clinical Opioid Withdrawal Symptom Scale (COWS) from baseline to 12 weeks
timeFrame: up to 12 weeks
measure: Change of craving from baseline in Visual Analog Scale (VAS) at 12 weeks
timeFrame: up to 12 weeks
measure: Change of self-reported euphoria after using heroin
timeFrame: up to 12 weeks
measure: Subjects ' overall evaluation of efficacy of relapse prevention treatment of thienorphine hydrochloride tablets
timeFrame: up to 12 weeks
measure: Researchers' overall evaluation of efficacy of relapse prevention treatment of thienorphine hydrochloride tablets
timeFrame: up to 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: The Second Xiangya Hospital，Central South University, Changsha, China
name: Weri Hao, Doctor
role: PRINCIPAL_INVESTIGATOR
References: