A Study of Cebranopadol for Opioid Withdrawal Symptoms in Adults With Chronic Pain

Key Inclusion Criteria:

* Adults 18-65 years with BMI 18.0-40.0 kg/m² and weight ≥50 kg.
* Chronic daily pain for ≥6 months due to chronic low back pain, hip/knee osteoarthritis, or painful peripheral neuropathy.
* Prescribed opioid use ≥5 days/week for ≥3 months within the prior 6 months, generally 50-90 MME/day; \>90 MME/day may be allowed with Sponsor/designee approval.
* Generally in good health and able to comply with study procedures, including opioid withdrawal and inpatient confinement.
* Meet protocol-specified reproductive and contraception requirements.
* Able to provide informed consent and complete study assessments in English.
* Physical opioid dependence confirmed by protocol-defined COWS and/or SOWS criteria before randomization.

Key Exclusion Criteria:

* Clinically significant medical or psychiatric condition that could compromise participant safety or study validity.
* Protocol-specified excluded pain, neurologic, spinal, infectious, or neoplasm-related conditions.
* QTcF \>450 ms in males or \>470 ms in females, other torsade de pointes risk factors, or use of QT-prolonging medications.
* Substance use disorder other than opioid, nicotine, or caffeine use disorder, or positive testing for prohibited drugs/alcohol, subject to the protocol-specified cannabinoid exception.
* Positive HIV, hepatitis B surface antigen, or hepatitis C antibody test.
* Suicidal ideation or active suicidality within the past 2 years.
* Use of prohibited medications or inability to meet protocol-specified medication washout requirements.
* Pregnant or breastfeeding or planning pregnancy within 30 days after the last study-drug dose.
* Significant adverse reaction to naloxone or related opioids/opioid antagonists.
* Unable to undergo IV catheter placement or otherwise considered unsuitable or unlikely to comply with the protocol.
* Legal, employment, or other circumstances that could interfere with study participation or compliance.