Acute PainPhase 3STARDOM1NCT02982161
Efficacy and Safety in a Randomised Acute Pain Study of MR308 (Tramadol/Celecoxib).
A Phase 3 study testing MR308 and Tramadol in people with Acute Pain, run by Mundipharma Research GmbH & Co KG at 7 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Pain
- What is being tested?
- MR308 and Tramadol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 818 participants
- Where
- 7 sitesin 6 countries
- Study dates
- 28 Dec 2016to 4 Jan 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male/female subjects ≥ 18 years on the day of consent.
- Willing and able to provide written informed consent for this study.
- 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.
- 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.
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- Additional Inclusion Criteria after Surgery:
- Third molar extractions 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 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.
Who cannot join
- 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.
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- Subjects who are in the Investigators opinion considered at increased risk of post-operative complications e.g. major dental infection/abscess.
- 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 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 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.
- Subjects who are incapable of complying with the protocol.
- Additional Exclusion Criteria after Surgery:
- 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.
- 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
- 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).
Trial locations and contacts
7 sites in 6 countries.
7 sites in 6 countries
Canada2 sites
Medical Arts Health Research Group
Penticton
Mount Sinai Hospital
Toronto
Poland1 site
POLIMEDICA Centrum Badań, Profilaktyki i Leczenia Sp. z o.o. Sp. k.
Zgierz
About this study
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).
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.
Read the 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.
- Conditions
- Acute Pain
- Being tested
- MR308, Tramadol, Placebo
- Keywords
- Third Molar Tooth Extraction
- Medical subject headings
- Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MR308Drug
Also called Tramadol/Celecoxib
Over-encapsulated tablet, Dosing frequency: two times daily, Mode of administration: oral
TramadolDrug
Also called Tramadol immediate release
Over-encapsulated capsule, Dosing frequency: four times daily, Mode of administration: oral
PlaceboDrug
Capsule, Dosing frequency: four times daily, Mode of administration: oral
| Study group | Role | What they receive |
|---|---|---|
| MR308 100 mg bid | Active comparator | Tramadol/Celecoxib 100 mg Receives: Drug: MR308 |
| MR308 150 mg bid | Active comparator | Tramadol/Celecoxib 150 mg Receives: Drug: MR308 |
| MR308 200 mg bid | Active comparator | Tramadol/Celecoxib 200 mg Receives: Drug: MR308 |
| Tramadol 100 mg qid | Active comparator | Tramadol IR 100 mg Receives: Drug: Tramadol |
| Placebo | Placebo comparator | Placebo to match MR308 and Tramadol IR Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of MR308 doses in the treatment of moderate to severe acute pain, based on the Sum of Pain Intensity Differences (SPID).
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.
Measured: 0-4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2016 (estimated)
- Study start28 Dec 2016
- Primary completion4 Jan 2018
- Study completion4 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 818 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mundipharma Research GmbH & Co KG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02982161
- Sponsor's protocol ID
- MR308-3501
- Acronym
- STARDOM1
- Status last verified
- May 2018
- First submitted
- 25 Nov 2016
- Last updated
- 29 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 39316284Langford R, Pogatzki-Zahn EM, Morte A, Sust M, Cebrecos J, Vaque A, Ortiz E, Fettiplace J, Adeyemi S, Lopez-Cedrun JL, Bescos S, Gascon N, Plata-Salaman C. Co-crystal of Tramadol-Celecoxib Versus Tramadol or Placebo for Acute Moderate-to-Severe Pain After Oral Surgery: Randomized, Double-Blind, Phase 3 Trial (STARDOM1). Adv Ther. 2024 Mar;41(3):1025-1045. doi: 10.1007/s12325-023-02744-2. Epub 2024 Jan 6.
PubMed 38183526
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT02982161
- Acronym / sponsor ID
- STARDOM1 / MR308-3501
- Conditions
- Acute Pain
- Keywords
- Third Molar Tooth Extraction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 818 participants (actual)
- Lead sponsor
- Mundipharma Research GmbH & Co KGIndustry (pharma, biotech, devices)
- Study start
- 28 Dec 2016 (actual)
- Primary completion
- 4 Jan 2018 (actual)
- Study completion
- 4 Jan 2018 (actual)
- First posted
- 5 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| MR308 100 mg bid | Active comparator | Drug: MR308Tramadol/Celecoxib 100 mg |
| MR308 150 mg bid | Active comparator | Drug: MR308Tramadol/Celecoxib 150 mg |
| MR308 200 mg bid | Active comparator | Drug: MR308Tramadol/Celecoxib 200 mg |
| Tramadol 100 mg qid | Active comparator | Drug: TramadolTramadol IR 100 mg |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo to match MR308 and Tramadol IR |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male/female subjects ≥ 18 years on the day of consent.
- Willing and able to provide written informed consent for this study.
- 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.
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MR308Also: Tramadol/CelecoxibOver-encapsulated tablet, Dosing frequency: two times daily, Mode of administration: oral | Drug | MR308 100 mg bid, MR308 150 mg bid, MR308 200 mg bid |
| TramadolAlso: Tramadol immediate releaseOver-encapsulated capsule, Dosing frequency: four times daily, Mode of administration: oral | Drug | Tramadol 100 mg qid |
| PlaceboCapsule, Dosing frequency: four times daily, Mode of administration: oral | Drug | Placebo |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2018.
- Derived from this study: PubMed 39316284Viscusi 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.
- Derived from this study: PubMed 38183526Langford R, Pogatzki-Zahn EM, Morte A, Sust M, Cebrecos J, Vaque A, Ortiz E, Fettiplace J, Adeyemi S, Lopez-Cedrun JL, Bescos S, Gascon N, Plata-Salaman C. Co-crystal of Tramadol-Celecoxib Versus Tramadol or Placebo for Acute Moderate-to-Severe Pain After Oral Surgery: Randomized, Double-Blind, Phase 3 Trial (STARDOM1). Adv Ther. 2024 Mar;41(3):1025-1045. doi: 10.1007/s12325-023-02744-2. Epub 2024 Jan 6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MR308 and Tramadol in people with Acute Pain, run by Mundipharma Research GmbH & Co KG at 7 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Canada, Germany, Hungary, Italy, Poland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02982161, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2018.