Efficacy and Safety in a Randomised Acute Pain Study of MR308: STARDOM2.

NCT03062644 | Completed Phase 3

• 1 other identifier: MR308-3502
• Study Type: interventional
• Target: 1,138
• Locations: 8 countries
• Sites: 8

Brief Summary

The MR308-3502 study is a multicenter double-blind, randomised, placebo- and active comparator-controlled study in female subjects to evaluate the efficacy and safety of MR308 with acute pain after TAH or STAH (total or subtotal abdominal hysterectomy).

Conditions

Acute Pain

Keywords

Open Total or Subtotal Abdominal Hysterectomy

Outcome Measures

Primary Outcomes (1)

• Efficacy of MR308 doses in the treatment of moderate to severe acute pain, based on the Sum of Pain Intensity Differences (SPID) from 0-4 hours.

  The primary efficacy endpoint is the Sum of Pain Intensity Differences over 0-4 hours (SPID4). SPID4 is derived as the weighted Sum of Pain Intensity Differences (baseline pain - current pain), measured at different time points via the PI-VAS. Time between two consecutive measurements will be used for weighting. Larger values indicate larger pain relief.

  0-4 hours

Study Arms (6)

MR308 100 mg bid

EXPERIMENTAL

Tramadol/Celecoxib)

Drug: MR308

MR308 150 mg bid

EXPERIMENTAL

Tramadol/Celecoxib

Drug: MR308

MR308 200 mg bid

EXPERIMENTAL

Tramadol/Celecoxib

Drug: MR308

Tramadol 100 mg qid

ACTIVE COMPARATOR

Tramadol

Drug: MR308

Celecoxib 100 mg bid

ACTIVE COMPARATOR

Celecoxib

Drug: MR308

Placebo

PLACEBO COMPARATOR

Placebo

Drug: MR308

Interventions

MR308 DRUG

two times daily; Mode of Administration:oral

Also known as: Tramadol/Celecoxib

MR308 100 mg bid; MR308 150 mg bid; MR308 200 mg bid

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female subjects ≥ 18 years on the day of consent.
• Willing and able to provide written informed consent for this study.
• Subjects are scheduled to have a total or subtotal abdominal hysterectomy under general anasethesia via a Pfannenstiel incision.
• 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.
• American Society Anaesthesiology physical status of I or II.
• 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).
• Good general health as judged by Investigators on the basis of medical history and physical examination.
• Willingness to comply with the study procedures and requirements.
• Abdominal hysterectomy completed without any immediate complication.
• Tolerating oral fluids, no uncontrolled nausea/vomiting and ready to take oral analgesia.
• The subject is alert and calm, spontaneously pays attention to caregiver, e.g. RASS = 0 (Sessler et al., 2002 \& Ely et al., 2003).
• 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.
• 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 24 hours after leaving the recovery room and subjects can only be randomised on the day after surgery, after cessation of the post-operative analgesia.

You may not qualify if:

• Any abnormal laboratory value that is clinically significant in the opinion of Investigator that would compromise the safety of the subject in the study.
• Any recent history of frequent nausea or vomiting, dizziness within the last 3 months regardless of etiology.
• 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.
• 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. anaphylactic shock, bronchospasm, angioedema) to any drugs.
• Subjects who are known to have had inadequate pain relief from paracetamol, tramadol or celecoxib.
• Subjects requiring any medication which is prohibited as per section prohibited medication.
• 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.
• 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.
• Significant neurological or psychiatric disorders including mental instability (unrelated to the pain) that could interfere with pain assessment; other pre-existing or new non-abdominal/pelvic pain that might impair the assessment of the nociceptive pain.
• 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.
• Previous randomisation in this study.
• 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).
• 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.
• Subjects who are incapable of complying with the protocol.
• Epidural or spinal anaesthesia or infiltration of the wound with an infusion of a local anaesthetic agent is not allowed. A single perioperative dose is allowed.

Sponsors & Collaborators

• Mundipharma Research GmbH & Co KG: lead

Study Sites (8)

Minsk City Gynecology Hospital Department of Gynecology

Minsk, 220007, Belarus

Location

"Multiprofile Hospital for Active Treatment - Doverie" AD, Sofia Department of Gynecology

Sofia, 1632, Bulgaria

Location

Victoria Hospital - London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Bajcsy-Zsilinszky Korhaz Szuleszet-Nogyogyaszati Osztaly

Budapest, 1106, Hungary

Location

Vidzeme Hospital Department of Gynecology and Obstetrics

Valmiera, 4201, Latvia

Location

Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu Oddział Ginekologii i Położnictwa

Przemyśl, 37-700, Poland

Location

Federal State Budgetary Institution National Medical-Surgical Centre named after N.I. Pirogov of the Ministry of Health of the Russian Federation Anesthesiology

Moscow, 105203, Russia

Location

Hospital Universitari Germans Trias i Pujol Anestesia y Reanimación

Barcelona, 08916, Spain

Location

Related Publications (2)

• Viscusi ER, Langford R, Morte A, Vaque A, Cebrecos J, Sust M, Gimenez-Arnau JM, de Leon-Casasola O. Safety of Co-Crystal of Tramadol-Celecoxib (CTC) in Patients with Acute Moderate-to-Severe Pain: Pooled Analysis of Three Phase 3 Randomized Trials. Pain Ther. 2024 Dec;13(6):1617-1631. doi: 10.1007/s40122-024-00655-w. Epub 2024 Sep 24.

  PMID: 39316284 DERIVED

• Langford R, Morte A, Sust M, Cebrecos J, Vaque A, Ortiz E, Fettiplace J, Adeyemi S, Raba G, But-Husaim L, Gascon N, Plata-Salaman C. Efficacy and safety of co-crystal of tramadol-celecoxib (CTC) in acute moderate-to-severe pain after abdominal hysterectomy: A randomized, double-blind, phase 3 trial (STARDOM2). Eur J Pain. 2022 Nov;26(10):2083-2096. doi: 10.1002/ejp.2021. Epub 2022 Sep 24.

  PMID: 35974668 DERIVED

MeSH Terms

Conditions

Acute Pain

Interventions

Tramadol; Celecoxib

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2017
• First Posted: February 23, 2017
• Study Start: April 5, 2017
• Primary Completion: June 29, 2018
• Study Completion: June 29, 2018
• Last Updated: September 20, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

LA (1); BU (1); RU (1); BE (1); CA (1); PL (1); ES (1); HU (1)