Chronic PainPhase 2NCT07874620
A Study of Cebranopadol for Opioid Withdrawal Symptoms in Adults With Chronic Pain
A Phase 2 study testing Cebranopadol in people with Chronic Pain and Pain, run by Adneuris Therapeutics, Inc. at 2 sites in United States.
Trial summary
This Phase 2 study will evaluate whether multiple doses of cebranopadol suppress opioid withdrawal signs and symptoms compared with placebo in adults with chronic pain who are physically dependent on prescribed opioids. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Pain, Pain, Opioid Withdrawal (Disorder)
- What is being tested?
- Cebranopadol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2026to Jun 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
00113
Houston, Texas, 77043
- Recruiting
001127
North Canton, Ohio, 44702
About this study
Official title: A Randomized, Double-Blind, Multiple-Dose Study to Assess the Ability of Cebranopadol to Suppress Withdrawal Signs and Symptoms in Adults With Chronic Pain Who Are Physically Dependent on Opioids
This Phase 2 study will evaluate whether multiple doses of cebranopadol suppress opioid withdrawal signs and symptoms compared with placebo in adults with chronic pain who are physically dependent on prescribed opioids. Participants whose physical dependence is confirmed will be assigned by chance to one of two cebranopadol dose regimens or matching placebo. The study will also evaluate pain, safety and tolerability, and cebranopadol pharmacokinetics.
Read the detailed description
Participants will complete outpatient screening followed by an inpatient treatment period and a safety follow-up telephone call. Within 30 days of initiating screening, participants will be admitted to the clinical research site.
Their current prescribed opioid will be withheld after the scheduled morning dose on Day -1, and withdrawal signs and symptoms will be assessed using the Clinical Opiate Withdrawal Scale (COWS) and Subjective Opioid Withdrawal Scale (SOWS) to confirm physical dependence. Participants meeting the predefined withdrawal criteria will resume their prescribed opioid as specified in the protocol and will subsequently be randomized on Day 1. Eligible participants will be randomized 1:1:1, stratified by current prescribed daily opioid regimen (50-75 morphine milligram equivalents [MME] versus >=76 MME), to cebranopadol 400 micrograms in the morning plus 200 micrograms in the evening, cebranopadol 400 micrograms twice daily, or matching placebo twice daily. Study drug is administered every 12 hours for 48 hours. Participants remain inpatient during treatment and undergo withdrawal, pain, safety, and pharmacokinetic assessments. Rescue medication is available according to protocol-defined criteria. Participants may resume their current prescribed opioid at least 12 hours after the final study-drug dose and are monitored until discharge on Day 4. A safety follow-up telephone call occurs on Day 7 (+/-2 days) after the last study-drug administration
- Conditions
- Chronic Pain, Pain, Opioid Withdrawal (Disorder), Opioid Use Disorder
- Being tested
- Cebranopadol, Placebo
- Keywords
- cebranopadol, opioid withdrawal;, physical dependence;, chronic pain;, Clinical Opiate Withdrawal Scale, COWS, Subjective Opioid Withdrawal Scale, SOWS Opioid use disorder, Subject Opioid Withdrawal scale
- Medical subject headings
- Chronic Pain, Pain, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CebranopadolDrug
Administration orally twice daily on Days 1 and 2 and according to the assigned regimen.
CebranopadolDrug
Administration orally twice daily on Days 1 and 2 and according to the assigned regimen.
PlaceboDrug
Administration orally twice daily on Day 1 and 2.
| Study group | Role | What they receive |
|---|---|---|
| Cebranopadol 600 micrograms/day | Experimental | Cebranopadol 400 micrograms orally in the morning and 200 micrograms orally in the evening on Day 1 and 2; final dose on the evening of Day 2 Receives: Drug: Cebranopadol |
| Cebranopadol 800 micrograms/day | Experimental | Cebranopadol 400 micrograms orally twice daily on Day 1 and 2; Final dose on the evening of Day 2. Receives: Drug: Cebranopadol |
| Placebo Comparator | Placebo comparator | Matching placebo orally twice daily on Day 1 and 2 days; Final dose on the evening of Day 2. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Opiate Withdrawal Scale (COWS) Total Score Maximum Effect (Emax) from 0 to 48 hours
Maximum (peak) COWS total score observed during the 48-hour assessment period. after the first study drug dose, using the protocol-specified adjustment for rescue medication. The COWS is an 11-item clinician-rated scale used to assess opioid withdrawal signs and symptoms. Total scores range from 0 to 48, with higher scores indicating greater withdrawal severity.
Measured: From first study-drug administration through 48 hours after the first dose]
Secondary outcomes (12)
Area under the curve of COWS Total Score from 0 to 48 hours (AUC0-48)
Area under the curve (AUC) of COWS total score-time curve from 0 to 48 hours after the first study drug dose, using the protocol-specified adjustment for rescue medication. COWS total scores range from 0 to 48, with higher scores indicating greater withdrawal severity.
Measured: From first study-drug administration through 48 hours after the first dose.
Proportion of Participants Meeting the COWS Responder Criteria
Proportion of participants meeting the protocol-defined COWS responder criteria based on average COWS total score and absence of opioid rescue medication through 24 hours.
A responder is defined as having at least 30 percent improvement and/or a COWS total score of 5 or less and/or transition to a lower withdrawal severity category from baseline, without opioid rescue medication through 24 hours.
Measured: From first study-drug administration through 24 hours after the first dose
Maximum Change From Baseline in COWS Total Score by Dosing Day.
Maximum change from baseline in COWS total score by dosing day during Day 1, Day 2.
Measured: Baseline- From first study-drug administration through 72 hours after the first dose
Area Under the Curve of COWS Total Score From 0 to 24 Hours (AUC0-24) COWS Total Score AUC0-24and From 0 to 72 Hours (AUC0-72).
Area under the curve (AUC) of COWS total scores, through 24 hours; and 72 hours after the first study drug dose, using the protocol-specified adjustment for rescue medication.
Measured: 0-24 hours and 0-72 hours after first study-drug administration
Maximum Subjective Opioid Withdrawal Scale (SOWS) Total Score.
Subjective Opioid Withdrawal Scale total score assessed using Emax, maximum change from baseline by dosing day, and area-under-the-curve summaries.
The SOWS is a participant-reported measure of opioid withdrawal symptoms. Total scores range from 0 to 64, with higher scores indicating greater withdrawal severity.
Measured: Through 72 hours after first study-drug administration]
Participants Receiving Rescue Medication
Proportion of participants who receive protocol-permitted rescue medication for withdrawal signs and symptoms.
Measured: Through the inpatient assessment period, up to 72 hours after first study-drug administration
Time to First Rescue Medication for Withdrawal
Time from first study-drug administration to first administration of protocol permitted rescue medication to manage withdrawal symptoms
Measured: Up to 72 hours after first study-drug administration
Opioid Rescue Medication Use
Number of opioid rescue medication doses and total opioid rescue medication use expressed in morphine milligram equivalents (MME).
Measured: Up to 72 hours after first study-drug administration]
Area Under the Curve of "Pain Right Now" Numeric Pain Rating Scale Score From 0 to 48 Hours (AUC0-48)
Area under the curve for of "Pain Right Now" Numerical Pain Rating Scale (NPRS) pain 'right now' scores from 0 to 48 hours after the first study drug dose, using the protocol-specified adjustment for rescue medication. NPRS scores range from 0 (no pain) to 10 (worst possible pain).
Measured: 0 to 48 hours after first study-drug administration
Proportion of Participants With at Least a 2-Point Improvement from Baseline in Average 24-Hour Pain.
Percentage of participants with at least a 2-point improvement from baseline in the NPRS rating of average pain during the previous 24 hours.
Measured: 0 to 72 hours after first study-drug administration
Change From Baseline in Average/Worst/Least Pain During the Previous 24 Hours
Change from baseline in participant-reported Average/Worst/Least pain during the previous 24 hours on NPRS.
Measured: 0 to 72 hours after first study drug administration
Non-Opioid Rescue Medication Use
Number of non-opioid rescue medication doses and total non-opioid rescue medication use summarized by medication type.
Measured: Up to 72 hours after first study-drug administration]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomized in a 1:1:1 ratio to two cebranopadol dose regimens or matching placebo.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Adneuris Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Khyati Mehta, Study director, Adneuris Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07874620
- Sponsor's protocol ID
- TRN-228-201
- Status last verified
- Oct 2026
- First submitted
- 8 Oct 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Ferreira-Valente MA, Pais-Ribeiro JL, Jensen MP. Validity of four pain intensity rating scales. Pain. 2011 Oct;152(10):2399-2404. doi: 10.1016/j.pain.2011.07.005.
PubMed 21856077Hjermstad MJ, Fayers PM, Haugen DF, Caraceni A, Hanks GW, Loge JH, Fainsinger R, Aass N, Kaasa S; European Palliative Care Research Collaborative (EPCRC). Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage. 2011 Jun;41(6):1073-93. doi: 10.1016/j.jpainsymman.2010.08.016.
PubMed 21621130Lofwall MR, Walsh SL, Bigelow GE, Strain EC. Modest opioid withdrawal suppression efficacy of oral tramadol in humans. Psychopharmacology (Berl). 2007 Oct;194(3):381-93. doi: 10.1007/s00213-007-0847-3. Epub 2007 Jul 1.
PubMed 17605004Lofwall MR, Babalonis S, Nuzzo PA, Elayi SC, Walsh SL. Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans. Drug Alcohol Depend. 2016 Jul 1;164:143-150. doi: 10.1016/j.drugalcdep.2016.05.002. Epub 2016 May 10.
PubMed 27234658Sigmon SC, Wong CJ, Chausmer AL, Liebson IA, Bigelow GE. Evaluation of an injection depot formulation of buprenorphine: placebo comparison. Addiction. 2004 Nov;99(11):1439-49. doi: 10.1111/j.1360-0443.2004.00834.x.
PubMed 15500597Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9. doi: 10.1080/02791072.2003.10400007.
PubMed 12924748