Biased Opioid Agonists for Treatment of Opioid Withdrawal in OUD

• Status: Recruiting
• Trial end date: 2022-09-30
• Target enrollment: 0
• Participant gender: All

Summary

Background:

People with opioid-use disorder (OUD) might benefit from having more treatment drugs to choose from. A new drug, TRV734, could be used like methadone to treat OUD. It might not have as many side effects.

Objective:

To test if TRV734 relieves withdrawal symptoms and has fewer side effects than oxycodone in people with OUD.

Eligibility:

People ages 18-75 who have been receiving daily treatment with methadone for opioid use disorder for at least 3 months

Design:

Participants will be screened under Protocol 415. They will be screened with:

Medical, social, and psychiatric history

Physical exam

Electrocardiogram (ECG). For this, sticky pads will be placed on the participant s chest to monitor their heartbeat.

Blood and urine tests

Participants will stay in a residential unit for 13-26 days.

Most days, participants will receive their regular daily dose of methadone.

On 4 or 5 occasions, 3-4 days apart, participants will skip two doses of methadone in a row. About 4 hours after they skip the second dose, they will have an IV catheter inserted with a needle so that blood samples can be taken. They will take capsules of either oxycodone, a placebo, or the study drug. They will have an ECG. They will complete questionnaires. Their blood pressure, pupil size, and alertness will be tested. They will then take their usual dose of methadone.

Participants will give daily urine and breath samples.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute on Drug Abuse (NIDA)
• Treatments: Analgesics, Opioid

Criteria

• INCLUSION CRITERIA:

Participants will be eligible for inclusion in the study if they meet the following criteria:

• Age between 18 and 75.

• Currently receiving daily treatment with methadone (dose range 75-120 mg/day) for opioid-use disorder (OUD) for at least 3 months.

• Willing to miss a dose of methadone (without supplementing with other opioids), and reporting having done so in the past without severe withdrawal symptoms on the first day-with severe defined here as any of the following: repeated vomiting, repeated bouts of diarrhea, or any other symptoms so painful or uncomfortable that the participant would not want to experience them several times in this study.

• Willing to provide blood samples through an intravenous catheter.

• For women of childbearing potential: must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the first study drug dose (active or placebo) AND agree to use an adequate method of contraception (Adequate methods of contraception for sexually active women are those who have a male sexual partner(s) who is surgically sterilized prior to inclusion; have a sexual partner(s) who is/are exclusively female; is using oral contraceptives (either combined or progesterone only) WITH a single-barrier method of contraception consisting of spermicide and condom or diaphragm; is using double-barrier contraception, specifically, a condom plus spermicide AND a female diaphragm or cervical cap; or is using an approved intrauterine device (IUD) with established efficacy.) to avoid pregnancy for a period of 3 months beginning from 30 days prior to first dose of study drug. Women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (Standard NIH Clinical Center criteria for menopause: -Women over age 55 who have not had a period for 1 year will be considered menopausal and do not need a pregnancy test, FSH test, or contraception.

• Women between 50-55, who have not had a period for 1 year, should have an FSH test. If their FSH level is more than 20, they will be considered menopausal and do not need pregnancy testing or contraception. If their FSH level is less than 20, they will need pregnancy testing and contraception as required by the protocol.

• Women between 45-50 who have not had a period for 1 year will need both an FSH test and a pregnancy test. If they are not pregnant and their FSH level is more than 20, they will be considered menopausal, and will not require contraception or additional pregnancy testing. If their FSH test is less than 20, they will need pregnancy testing and contraception as required by the protocol.).

• For men, unless surgically sterilized (vasectomy with documentation of azoospermia), must agree to practice abstinence or use barrier contraception, and not donate sperm, for a period of 3 months beginning from first dose of study drug.

(6) Self-report of experiencing noticeable opioid withdrawal after missing just one or two days of methadone; this will be operationalized with the screening question: How many days of methadone do you have to miss before you have withdrawal symptoms such as runny nose, nausea, aches, chills, or anxiety?

EXCLUSION CRITERIA:

Applicants will not be eligible if they meet any of the following criteria:

• History of DSM-5 psychotic or bipolar disorder; current DSM-5 Major Depressive Disorder.

• Current DSM-5 dependence on alcohol or sedative-hypnotic, e.g. benzodiazepine.

• cognitive impairment severe enough to preclude informed consent or valid self-report.

• any condition that interferes with urine or blood sampling.

• medical illness or medications that, in the view of the investigators, would compromise participation in research, including but not limited to pulmonary disease, cirrhosis, nephrotic syndrome, thyroid disease, epilepsy, panhypopituatarism, adrenal insufficiency, ischemic heart disease, history of QTc prolongation, prolonged QT on screening ECG (men, >450ms; women, > 470ms), and potential causes of QTc prolongation (electrolyte abnormalities such as hypokalemia, hypomagnesemia, and hypocalcemia; medications such as certain antihistamines, antiemetics, antiarrhythmics, antidepressants, antibiotics, and antipsychotics; and structural or functional heart disease such as congenital long QT syndrome).

• medications that could alter the effects of the opioid agonists being studied, including CYP3A4 inhibitors or inducers.

• For women: pregnancy or breastfeeding.

• Any of the following lab values: Hb < 10; Cr >2.0; AST or ALT >3x upper limit of normal; total bilirubin >2.0.

• Any other medical reason or clinical condition that the study physician considers unsafe for participation in the study.