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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03062644
• Date of registration: 20/02/2017
• Prospective Registration: Yes
• Primary sponsor: Mundipharma Research GmbH & Co KG
• Public title: Efficacy and Safety in a Randomised Acute Pain Study of MR308: STARDOM2. STARDOM2
• Scientific 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 Abdominal Hysterectomy Surgery Under General Anaesthesia (STARDOM2).
• Date of first enrolment: April 5, 2017
• Target sample size: 1138
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03062644
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Belarus, Bulgaria, Canada, Czech Republic, Germany, Hungary, Japan, Latvia, Lithuania, Poland, Romania, Russian Federation, Slovakia, Spain

Key inclusion & exclusion criteria

Inclusion Criteria:

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 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.

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 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 pre-existing
or new non-abdominal/pelvic 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 are incapable of complying with the protocol.

15. 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.

16. History or ongoing chronic pelvic inflammatory disease or painful endometriosis.

17. History of advanced gynaecological cancers.

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 have not had the abdominal hysterectomy surgery completed as
planned.

2. If in the Investigator's opinion, there are any factors that may affect compliance
with the protocol.

3. Subject clinical need for antiemetics (apart from standard perioperative practice as


Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Acute Pain

Intervention(s)

Drug: MR308

Primary Outcome(s)

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. [Time Frame: 0-4 hours]

Secondary ID(s)

MR308-3502

Source(s) of Monetary Support

Please refer to primary and secondary sponsors