Efficacy and Safety in a randomised acute pain study of MR308.

Phase 1

• Conditions: Acute pain after open total or subtotal abdominal hysterectomy; MedDRA version: 20.1 Level: LLT Classification code 10066714 Term: Acute pain System Organ Class: 100000004867; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

• Registration Number: EUCTR2016-000593-38-BG
• Lead Sponsor: Mundipharma Research GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-03-02
• Study Completion: 2018-06-29
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 1138

Inclusion Criteria

Only subjects meeting all of the following inclusion criteria will be considered for study inclusion:
1. Female subjects = 18 years on the day of consent.
2. Willing and able to provide written informed consent for this study.
3. Subjects are scheduled to have a total or subtotal abdominal hysterectomy under general anasethesia via a Pfannenstiel incision.
4. The elective procedure (total or subtotal hysterectomy with or without salpingo-oophorectomy) must be for benign conditions within 28 days of screening. Subjects with stage 0 carcinoma in situ of cervix, endometrial hyperplasia or clinically staged 1A or 1B endometrial cancer are allowed to participate.
5. American Society Anaesthesiology physical status of I or II.
6. If a female is of child-bearing potential, she must be using highly effective methods of contraception throughout the study, not breastfeeding, and have negative pregnancy tests prior to receiving IMP. A highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasectomised partner).
7. Good general health as judged by Investigators on the basis of medical history and physical examination.
8. Willingness to comply with the study procedures and requirements.

Additional Inclusion Criteria after Surgery:

1. Abdominal hysterectomy completed without any immediate complication.
2. Tolerating oral fluids, no uncontrolled nausea/vomiting and ready to take oral analgesia.
3. The subject is alert and calm, spontaneously pays attention to caregiver, e.g. RASS = 0 (Sessler et al., 2002 & Ely et al., 2003).
4. Subjects will be capable to sit up from supine, stand up from a sitting position and walk 10 meters without assistance in the morning of the day following surgery.
5. Subjects with moderate or severe pain (qualifying PI-VAS score = 45mm and < 70mm or = 70mm and = 90mm) as a result of a surgical procedure (abdominal hysterectomy) under general anaesthesia. This must be measured within a maximum of 30 hours after end of surgery and subjects can only be randomized on the day after surgery, after cessation of the postoperative analgesia*.

*Randomisation within one pain group may be temporarily closed, please see section 11.4 for further Details.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Subjects having any of the following criteria must not be included in the study.
1. Any abnormal laboratory value that is clinically significant in the opinion of Investigator that would compromise the safety of the subject in the study.
2. Any recent history of frequent nausea or vomiting, dizziness within the last 3 months regardless of etiology.
3. Subjects having any medical condition or treatment that is either a warning or contraindication as per the SmPC of tramadol (e.g. selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, MAO inhibitors (within 14 days before taking IMP), antipsychotics, anticonvulsant and other seizure threshold-lowering medicinal products), celecoxib (e.g. increased risk of post-operative bleeding, active peptic ulceration, GI bleeding or inflammatory bowel disease) or paracetamol.
4. Known sensitivity and/or contraindication to tramadol, celecoxib, paracetamol, sulfonamides, opioids, NSAIDS, COX-2 inhibitors, or related compounds or formulation excipients as well as severe hypersensitivity reactions (e.g. angioedema) to any drugs.
5. Subjects who are known to have had inadequate pain relief from paracetamol, tramadol or celecoxib.
6. Subjects requiring any medication which is prohibited as per section prohibited medication.
7. Subjects who are in the Investigator’s opinion considered at increased risk of operative (those associated with the surgical procedure and general anaesthesia) and post-operative complications, e.g.excessive post-operative bleeding, infection.
8. Any history of drug or alcohol abuse, misuse, physical or psychological dependence, mood changes, sleep disturbance and functional capacity which have an impact on pain perception.
9. Significant neurological or psychiatric disorders including mental instability (unrelated to the pain) that could interfere with pain assessment; other pain that might impair the assessment of the nociceptive pain.
10. Any medical history of significant and/or inadequately controlled cardiovascular (uncontrolled high blood pressure, high risk of cardiovascular events, severe heart failure), pulmonary, hematologic, (including coagulopathy/bleeding disorders), neurological (e.g. subjects with epilepsy or those susceptible to seizures), liver disease (e.g. severe hepatic impairment), kidney disease (e.g. serum creatinine level greater than 1.5 times the upper limit of normal, impaired renal function in subjects taking diuretics, ACE-inhibitors, or angiotensin II antagonists), endocrine, immunologic, dermatologic painful conditions or any other conditions that may compromise the ability of the subject to participate in the study or might interfere with drug absorption, distribution, metabolism or excretion.
11. Previous randomisation in this study.
12. Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days of study entry (defined as the start of the Screening Period).
13. Subjects who were treated regularly with opioid analgesic or NSAIDs within 30 days prior to screening or who have received a long-acting NSAID within three days prior to the start of the surgery.
14. S

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified