Acute Pain, Bunionectomy
Conditions
Brief summary
This is a Phase 2 clinical trial of GRT7040, currently being developed for the treatment of moderate-to-severe acute pain. The primary purpose of this trial is to assess efficacy and safety of GRT7040 compared with placebo in adult participants with acute pain following bunionectomy. The trial will compare three different doses of GRT7040 given from Day 1 until Day 3 (eg, 48 h after the first investigational medicinal product \[IMP\] administration) of GRT7040 or placebo.
Detailed description
This is a randomized, double-blind, double-dummy, placebo- and active controlled, 2-part Phase 2 trial. In Part A, there will be three trial arms. In Part B there will be five trial arms. The trial duration for Parts A and B will be approximately 6 weeks (notwithstanding visit windows) consisting of a Screening Period (up to 28 Days), randomization and IMP administration on Day 1, followed by a 48 h of Treatment Period, and a 10-day Safety Follow-up (SFU) Period. Excluding the Screening Period, each participant will participate in the trial for approximately 13 (± 2) days (from Day 1 to the End-of-Trial \[EoT\] Visit). Screening will occur within 28 days before administration of the IMP. Informed consent will be obtained prior to performing any trial-related procedures or assessments.
Interventions
DRUGGRT7040
The trial will compare three different doses of GRT7040 (Low, Medium \[Mid\] and High doses)
DRUGHydrocodone bitartrate/ acetaminophen (HB/APAP)
Reference drug
Dummy treatment
DRUGPlacebo (matched to GRT7040)
Dummy treatment
Sponsors
Grünenthal GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults scheduled for a primary unilateral bunionectomy with distal first metatarsal osteotomy and internal fixation under regional anesthesia. * Able and willing to provide informed consent and comply with study procedures. * Body weight ≥50 kg and BMI 18 to 40 kg/m². * Medically fit for surgery and study treatment based on medical history, physical examination, ECG, vital signs, and laboratory assessments. * Meets protocol-specified contraception requirements. * After surgery, reports moderate to severe pain (Verbal Rating Scale) with a Numeric Pain Rating Scale (NPRS) score ≥4 within 9 hours after removal of the popliteal sciatic block. * Able to follow commands and has complied with protocol-required perioperative analgesic guidelines.
Exclusion criteria
* Clinically significant medical conditions or laboratory abnormalities that could increase risk or interfere with study assessments. * Major surgery within 6 months prior to screening or anticipated need for major surgery during the study. * Prior bunionectomy or related surgery on either applicable foot. * Peripheral neuropathy affecting the legs. * Clinically significant cardiac disease, arrhythmias, QT prolongation risk, or abnormal ECG findings. * Sleep apnea requiring positive airway pressure therapy. * American Society of Anesthesiologists (ASA) physical status classification ≥3. * Contraindication, intolerance, allergy, or unwillingness to receive study-related analgesics, NSAIDs, acetaminophen/hydrocodone, local anesthetics, or study drug components. * Participation in another interventional clinical trial within the protocol-defined exclusion period. * Significant renal impairment, hepatic impairment, positive HIV, hepatitis B, or hepatitis C tests. * History of substance abuse or addiction within the previous 3 years or positive drug/alcohol screening as specified by the protocol. * Blood or plasma donation exceeding protocol limits before screening. * Pregnant, breastfeeding, planning pregnancy during the study, or unwilling to comply with contraception requirements. * Postoperative factors precluding randomization, including unsuccessful popliteal block placement, surgical complications, non-adherence to postoperative analgesic requirements, or medical complications during surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-Weighted Sum of Pain Intensity Difference From 0 to 48 Hours (SPID48) | Baseline to 48 hours after first dose of IMP | Time-weighted sum of the pain intensity difference as recorded on a Numeric Pain Rating Scale (NPRS) (from 0 = no pain to 10 = pain as bad as you can imagine) from 0 to 48 hours after the first dose of IMP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | From first dose of IMP through End of Treatment visit (Day 13 ± 2 days) | To assess the safety and tolerability of GRT7040 |
| Time-Weighted Sum of Pain Intensity Difference From 0 to 24 Hours (SPID24) | Baseline to 24 hours after first dose of IMP | Time-weighted sum of the pain intensity difference as recorded on a NPRS (from 0 = no pain to 10 = pain as bad as you can imagine) from 0 to 24 hours after the first dose of IMP. |
| Time-Weighted Sum of Pain Intensity Difference From 4 to 48 Hours (SPID4-48) | 4 to 48 hours after first dose of IMP | Time-weighted sum of the pain intensity difference as recorded on a NPRS (from 0 = no pain to 10 = pain as bad as you can imagine) from 4 to 48 hours after the first dose of IMP. |
| Participants With ≥30%, ≥50%, and ≥70% Reduction in Pain From Baseline | At 12, 24, and 48 hours after first dose of IMP | Percentage of participants with ≥30%, ≥50%, and ≥70% reduction in pain from Baseline as measured by a NPRS (from 0 = no pain to 10 = pain as bad as you can imagine) at 12, 24, and 48 hours. |
| Time to ≥2 point Reduction in Pain From Baseline | From first dose of IMP through 48 hours after first dose | Time to a ≥2 point reduction in pain from Baseline as measured by a NPRS (from 0 = no pain to 10 = pain as bad as you can imagine) after the first dose of IMP. |
| Time to First Rescue Medication Use | From first dose of IMP through 48 hours after first dose | Time to first rescue medication use after the first dose of IMP. |
| Percentage of participants using rescue medication | From first dose of IMP through 48 hours after first dose | Percentage of participants using rescue medication 0 to 48 h after the first dose of IMP. |
| Total rescue medication use | From first dose of IMP through 48 hours after first dose | Total rescue medication use 0 to 48 h after the first dose GRT7040 versus placebo |
| Participants Reporting "Good" or "Excellent" on the Patient Global Assessment | At 24 and 48 hours after first dose of IMP | Proportion of participants reporting "Good" or "Excellent" on the Patient Global Assessment at 24 and 48 hours after the first dose of IMP. |
| Time to Perceptible Pain Relief and Meaningful Pain Relief | From first dose of IMP through 24 hours after first dose | Time to onset of perceptible pain relief and meaningful pain relief assessed using the double-stopwatch method after the first dose of IMP |
Contacts
CONTACTGrünenthal Clinical Trial Helpdesk
Outcome results
None listed