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Trial record 6 of 7 for:    TRAMADOL | ( Map: Germany )

Efficacy and Safety in a Randomised Acute Pain Study of MR308 (Tramadol/Celecoxib). (STARDOM1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02982161
Recruitment Status : Completed
First Posted : December 5, 2016
Last Update Posted : May 29, 2018
Information provided by (Responsible Party):
Mundipharma Research GmbH & Co KG

Brief Summary:
The MR308-3501 study is a multicenter, randomised, double-blind, parallel-group study in male and female adult subjects to demonstrate the efficacy of MR308 in the treatment of acute moderate to severe pain after the extraction of at least two third molars requiring bone removal.

Condition or disease Intervention/treatment Phase
Acute Pain Drug: MR308 Drug: Tramadol Drug: Placebo Phase 3

Detailed Description:

This is a multicenter double-blind, randomised, phase III study in male and female subjects with acute pain after third molar tooth extraction. The dental procedure must have involved extraction of at least two impacted third molars requiring bone removal. If only two impacted third molars are extracted, they must be ipsilateral and both require bone removal under local anaesthesia.

The Screening Visit (Visit 1) can take place up to 28 days before the planned third molar extractions. The randomisation visit (Visit 2) consists of three different sections, a part before the surgery, the part with the surgery and before randomisation, and a part with the randomisation and post-randomisation assessments. The visits 3 and 4, one respectively two days after the randomisation can be performed by telephone if the subject does not participate in the pharmacokinetic sampling.

The last dose of IMP should be taken by the subject about 72h after the initial dose and before the Completion/Discontinuation Visit (Visit 5) is performed.

The Adverse Event (AE) Follow-up Visit (Visit 6) is the last study visit and should not be done earlier than seven days after the subject's last dose of IMP. It can be performed by telephone.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 818 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Multicenter, Placebo- and Active Comparator-Controlled Study to Evaluate Efficacy and Safety of MR308 in the Treatment of Acute Pain After Third Molar Tooth Extraction (STARDOM1).
Actual Study Start Date : December 28, 2016
Actual Primary Completion Date : January 4, 2018
Actual Study Completion Date : January 4, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: MR308 100 mg bid
Tramadol/Celecoxib 100 mg
Drug: MR308
Over-encapsulated tablet, Dosing frequency: two times daily, Mode of administration: oral
Other Name: Tramadol/Celecoxib

Active Comparator: MR308 150 mg bid
Tramadol/Celecoxib 150 mg
Drug: MR308
Over-encapsulated tablet, Dosing frequency: two times daily, Mode of administration: oral
Other Name: Tramadol/Celecoxib

Active Comparator: MR308 200 mg bid
Tramadol/Celecoxib 200 mg
Drug: MR308
Over-encapsulated tablet, Dosing frequency: two times daily, Mode of administration: oral
Other Name: Tramadol/Celecoxib

Active Comparator: Tramadol 100 mg qid
Tramadol IR 100 mg
Drug: Tramadol
Over-encapsulated capsule, Dosing frequency: four times daily, Mode of administration: oral
Other Name: Tramadol immediate release

Placebo Comparator: Placebo
Placebo to match MR308 and Tramadol IR
Drug: Placebo
Capsule, Dosing frequency: four times daily, Mode of administration: oral

Primary Outcome Measures :
  1. Efficacy of MR308 doses in the treatment of moderate to severe acute pain, based on the Sum of Pain Intensity Differences (SPID). [ Time Frame: 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male/female subjects ≥ 18 years on the day of consent.
  2. Willing and able to provide written informed consent for this study.
  3. Subjects must have a planned elective dental procedure i.e. extraction of at least two impacted third molars (one of them must be mandibular) requiring bone removal, within 28 days after the Screening Visit. If only two impacted third molars are extracted, they must be ipsilateral and require bone removal.
  4. 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).
  5. Good general health as judged by Investigators on the basis of medical history and physical examination.
  6. Willingness to comply with the study procedures and requirements.

Additional Inclusion Criteria after Surgery:

  1. Third molar extractions 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 with moderate or severe pain (qualifying PI-VAS score ≥ 45mm and < 70mm or ≥ 70mm) as a result of an oral surgical procedure under local anaesthesia and/or sedation*. This must be measured within a maximum of 6 hours after the end of the surgical procedure.

Exclusion Criteria:

  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. anaphylactic shock, bronchospasm, 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 Investigators opinion considered at increased risk of post-operative complications e.g. major dental infection/abscess.
  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. Subjects who have received any analgesic medication (e.g. NSAIDs, oral opioid preparations etc.) other than short-acting preoperative or intraoperative local anaesthetic agents within 12 hours before the start of the surgery or peri operatively until randomisation.
  15. Subjects who are incapable of complying with the protocol.

Additional Exclusion Criteria after Surgery:

  1. Serious complication during surgery and up to randomisation, including:

    • Post-operative primary and secondary bleed that cannot be controlled.
    • Subjects who did not had the third molar extraction completed as planned.
  2. Post-operative medications or treatments that can have an analgesic effect or cause sedation or have amnesic effect are not permitted as these may interfere with the study assessments. These include use of ice packs, corticosteroids, nitrous oxide, benzodiazepines, alcohol, hypnotics, analgesics, opioids, other psychotropic medicinal products and any other analgesia except the provided study treatments
  3. If in the Investigators opinion there are any factors that may confound the analysis of the study regarding efficacy and safety (e.g. a PI-VAS score greater than 90).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02982161

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Medical Arts Health Research Group
Penticton, Canada
Mount Sinai Hospital
Toronto, Canada
University Hospital Greifswald
Greifswald, Germany
Semmelweis Egyetem Fogorvostudomnyi Kar
Budapest, Hungary
Policlinico G.B. Rossi
Verona, Italy
POLIMEDICA Centrum Badań, Profilaktyki i Leczenia Sp. z o.o. Sp. k.
Zgierz, Poland
Facultad de Odontología, Universitat de Barcelona
Barcelona, Spain
Sponsors and Collaborators
Mundipharma Research GmbH & Co KG

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Responsible Party: Mundipharma Research GmbH & Co KG Identifier: NCT02982161    
Other Study ID Numbers: MR308-3501
First Posted: December 5, 2016    Key Record Dates
Last Update Posted: May 29, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Mundipharma Research GmbH & Co KG:
Third Molar Tooth Extraction
Additional relevant MeSH terms:
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Acute Pain
Neurologic Manifestations
Signs and Symptoms
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Central Nervous System Depressants