Dysport in Post-Surgical Neuralgia (PMOD03)

Ipsen

Status and phase: Completed; Phase 2

Conditions: Chronic Scar Pain

Treatments: Biological: Botulinum toxin type A; Drug: Placebo; Drug: Lidocaine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03663101

2018-001703-37 (EudraCT Number)

D-FR-52120-244

Details and patient eligibility

About

The study is designed to determine whether a currently licensed version of botulinum toxin (Dysport®) is effective for the treatment of pain that has developed and/or persisted for months or years around the scar of a previous surgical site, and whether this condition could be suitable for the testing of similar new medicines. The study will compare three different doses of Dysport® to see if there is benefit and/or a best dose for treating persistent post-surgery scar pain.

Enrollment: 16 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female subjects aged between 18 and 75 years inclusive at the time of giving informed consent.
• Subjects suffering from an area of chronic pain post-abdominal or thoracic surgery, chronic abdominal or thoracic scar pain.
• Longitudinal axis of the pain area of 10 cm long maximum (as mapped upon screening).
• Subjects with moderate to severe pain, i.e. spontaneous NRS score of 4-8 which has been stable for the previous month before screening.
• Stable use of analgesics (or any medication impacting pain perception) during the month before screening and expected to be stable for the study duration.
• Under stable medication regimen for other medication, i.e. during the month before screening.
• Time from surgery which caused the painful scar more than six months and less than ten years at screening.
• No other distracting pain either chronic or acute.
• Female subjects of childbearing potential must have a negative urine pregnancy test result and be willing to use reliable contraceptive measures throughout study participation.
• The subject's primary care physician has provided evidence which can be used to confirm that within the last 12 months of dosing that there is nothing in their medical history that would preclude their enrolment into a clinical study.

Exclusion criteria

• Previous treatment with Botulinum neurotoxin (BTX) (any serotype) during the past six months before screening.
• History of hypersensitivity to any of the components of the Dysport formulation (which includes human serum albumin and lactose) or allergy to cow's milk protein.
• Known hypersensitivity to lidocaine or other anaesthetics of the amide type, known hypersensitivity to hydroxybenzoates, complete heart block, hypovolaemia.
• Any medical condition that may put the subject at risk with exposure to BTX, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disease that might interfere with neuromuscular function.
• Opioid analgesic use at a Morphine Equivalent Dosage (MED) of >75mg per day.
• Neuroma in the scar pain area, diagnosed per ultrasound.
• Use of agents that could interfere with neuromuscular transmission, including calcium channel blockers, penicillamine, aminoglycosides, lincosamides, polymixins, magnesium sulphate, anticholinesterases, succinylcholine and quinidine.
• Need of any prohibited medication.
• Any abnormal laboratory value, physical examination, vital signs, or electrocardiogram (ECG) that, in the opinion of the investigator, is clinically significant and that would compromise the safety of the subject in the study.
• Positive for hepatitis B antigen or hepatitis C virus ribonucleic acid, positive results for human immunodeficiency virus, or who receives diagnosis for acquired immunodeficiency syndrome.
• Positive urine screen for drugs of abuse (except for cotinine and unless explained by the investigator for therapeutic use of medication) or 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 assessments; other pre-existing pain syndromes, acute or chronic, that might impair the assessment of the scar pain.
• Any medical history of significance and/or inadequately controlled such as cardiovascular (e.g. uncontrolled high blood pressure, high risk of cardiovascular events, severe heart failure), pulmonary (e.g. uncontrolled asthma or emphysema), haematologic, (e.g. coagulopathy/bleeding disorders), neurological (e.g. swallowing problems, blurred or double vision, trouble saying words clearly (dysarthria), hoarseness or change or loss of voice (dysphonia)), liver disease (e.g. severe hepatic impairment), kidney disease (e.g. impaired renal function in subjects taking diuretics, angiotensin converting enzyme (ACE)-inhibitors, or angiotensin II antagonists), endocrine, immunologic, dermatologic painful conditions or any other conditions that may compromise in the opinion of the investigator the ability of the subject to participate in the study.
• Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days before screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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16 participants in 5 patient groups, including a placebo group

Pre-Randomization, Run-In period (part A)

Experimental group

Description:

Crossover run-in part A - Subjects will be injected (Test 1) with either saline or local anaesthetic (lidocaine). One week later, they will be crossed over, injected with the other agent (Test 2).

Treatment:

Drug: Placebo

Drug: Lidocaine

Drug: Placebo

Dysport dose 1 (part B)

Experimental group

Description:

Dysport dose 1 as a single-dose, intradermal injection.

Treatment:

Biological: Botulinum toxin type A

Dysport dose 2 (part B)

Experimental group

Description:

Dysport dose 2 as a single-dose, intradermal injection.

Treatment:

Biological: Botulinum toxin type A

Dysport dose 3 (part B)

Experimental group

Description:

Dysport dose 3 as a single-dose, intradermal injection.

Treatment:

Biological: Botulinum toxin type A

Placebo (saline solution) (part B)

Placebo Comparator group

Description:

Placebo single-dose, intradermal injection.

Treatment:

Drug: Placebo

Drug: Placebo