Chronic Pain, Pain, Opioid Withdrawal (Disorder), Opioid Use Disorder
Conditions
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
Brief 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. 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.
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
Interventions
DRUGCebranopadol
Administration orally twice daily on Days 1 and 2 and according to the assigned regimen.
DRUGPlacebo
Administration orally twice daily on Day 1 and 2.
Sponsors
Adneuris Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants, investigators, investigator-site personnel, service-provider personnel, and sponsor or designee personnel are masked, except designated unblinded personnel involved in study-drug management, compliance auditing, or randomization-code generation. Study treatments are identical in appearance and over-encapsulated. Prescribed opioids and rescue medications are administered unblinded
Intervention model description
Participants are randomized in a 1:1:1 ratio to two cebranopadol dose regimens or matching placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Opiate Withdrawal Scale (COWS) Total Score Maximum Effect (Emax) from 0 to 48 hours | From first study-drug administration through 48 hours after the first dose] | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve of COWS Total Score from 0 to 48 hours (AUC0-48) | From first study-drug administration through 48 hours after the first dose. | 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. |
| Proportion of Participants Meeting the COWS Responder Criteria | From first study-drug administration through 24 hours after the first dose | 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. |
| Maximum Change From Baseline in COWS Total Score by Dosing Day. | Baseline- From first study-drug administration through 72 hours after the first dose | Maximum change from baseline in COWS total score by dosing day during Day 1, Day 2. |
| 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). | 0-24 hours and 0-72 hours after first study-drug administration | 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. |
| Maximum Subjective Opioid Withdrawal Scale (SOWS) Total Score. | Through 72 hours after first study-drug administration] | 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. |
| Participants Receiving Rescue Medication | Through the inpatient assessment period, up to 72 hours after first study-drug administration | Proportion of participants who receive protocol-permitted rescue medication for withdrawal signs and symptoms. |
| Time to First Rescue Medication for Withdrawal | Up to 72 hours after first study-drug administration | Time from first study-drug administration to first administration of protocol permitted rescue medication to manage withdrawal symptoms |
| Opioid Rescue Medication Use | Up to 72 hours after first study-drug administration] | Number of opioid rescue medication doses and total opioid rescue medication use expressed in morphine milligram equivalents (MME). |
| Area Under the Curve of "Pain Right Now" Numeric Pain Rating Scale Score From 0 to 48 Hours (AUC0-48) | 0 to 48 hours after first study-drug administration | 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). |
| Proportion of Participants With at Least a 2-Point Improvement from Baseline in Average 24-Hour Pain. | 0 to 72 hours after first study-drug administration | Percentage of participants with at least a 2-point improvement from baseline in the NPRS rating of average pain during the previous 24 hours. |
| Change From Baseline in Average/Worst/Least Pain During the Previous 24 Hours | 0 to 72 hours after first study drug administration | Change from baseline in participant-reported Average/Worst/Least pain during the previous 24 hours on NPRS. |
| Non-Opioid Rescue Medication Use | Up to 72 hours after first study-drug administration] | Number of non-opioid rescue medication doses and total non-opioid rescue medication use summarized by medication type. |
Countries
United States
Contacts
CONTACTStudy Director Adneuris Therapeutics
CONTACTClinical Development Adneuris Therapeutics
STUDY_DIRECTORKhyati Mehta
Adneuris Therapeutics
Outcome results
None listed