Overview

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.