Dysport in Post-Surgical Neuralgia | NCT03663101

NCT03663101

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2018-001703-37	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pre-Randomization, Run-In period (part A)	Experimental	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).	Drug: Lidocaine Drug: Placebo
Dysport dose 1 (part B)	Experimental	Dysport dose 1 as a single-dose, intradermal injection.	Biological: Botulinum toxin type A
Dysport dose 2 (part B)	Experimental	Dysport dose 2 as a single-dose, intradermal injection.	Biological: Botulinum toxin type A
Dysport dose 3 (part B)	Experimental	Dysport dose 3 as a single-dose, intradermal injection.	Biological: Botulinum toxin type A
Placebo (saline solution) (part B)	Placebo Comparator	Placebo single-dose, intradermal injection.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Lidocaine	Drug	0.5 mL (2.5 mg) of lidocaine per injection point will be injected subcutaneously (maximum 10 injection points).	Pre-Randomization, Run-In period (part A)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time to Onset of Effect in the Spontaneous Numerical Rating Scale (NRS) Score	The time to onset of effect was defined as the time to a decrease from baseline of two points or greater in the spontaneous NRS score. Pain intensity was scored using an 11-point NRS score ranging from 0 to 10, where 0= no pain and 10= worst possible pain. Participants were provided with an Actiwatch® during an Actiwatch® training visit to record their spontaneous NRS scores at home. The Actiwatch® alerted the participants twice a day to record their average and maximal NRS scores over the preceding 12 hours. The questions were asked of the participants by the Actiwatch®: "Please rate your pain by selecting the one number that best describes your pain on average during the last 12 hours." and "Please rate your pain by selecting the one number that best describes your pain at its worst during the last 12 hours." Only descriptive statistical analysis was performed for this outcome measure.	Part B: From baseline (defined as mean of all predose data from Day -7 and including predose on Day 1) up to end of study (Week 16) or early discontinuation.
Peak Effect in the Spontaneous NRS Score	The peak effect was defined as the maximal decrease from baseline in the spontaneous NRS score over a 12-hour period. Pain intensity was scored using an 11-point NRS score ranging from 0 to 10, where 0= no pain and 10= worst possible pain. Participants were provided with an Actiwatch® during an Actiwatch® training visit to record their spontaneous NRS scores at home. The Actiwatch® alerted the participants twice a day to record their average and maximal NRS scores over the preceding 12 hours. The questions were asked of the participants by the Actiwatch®: "Please rate your pain by selecting the one number that best describes your pain on average during the last 12 hours." and "Please rate your pain by selecting the one number that best describes your pain at its worst during the last 12 hours." Greater reductions in change from baseline correspond to greater pain relief.	Part B: From baseline (defined as mean of all predose data from Day -7 and including predose on Day 1) up to end of study (Week 16) or early discontinuation.
Time to Peak Effect in the Spontaneous NRS Score

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Spontaneous NRS Score Throughout the Study	Pain intensity was scored using an 11-point NRS score ranging from 0 to 10, where 0= no pain and 10= worst possible pain. Participants were provided with an Actiwatch® during an Actiwatch® training visit to record their spontaneous NRS scores at home. The Actiwatch® alerted the participants twice a day to record their average and maximal NRS scores over the preceding 12 hours. The questions were asked of the participants by the Actiwatch®: "Please rate your pain by selecting the one number that best describes your pain on average during the last 12 hours." and "Please rate your pain by selecting the one number that best describes your pain at its worst during the last 12 hours." Greater reductions in change from baseline correspond to greater pain relief.

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Ipsen Medical Director	Ipsen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
St Pancras Clinical Research		London		WC1X8QD	United Kingdom

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received a single dose of placebo (matching with Dysport) intradermal injection per injection point (maximum of 10 injection points) on Day 1. Injections were performed under a constant volume of 0.2 milliliters (mL).
FG001	Dysport 2.5 U/Injection Site	Participants received a single dose of Dysport 2.5 units (U) intradermal injection per injection point (maximum of 10 injection points) on Day 1. The maximal total dose was 25 U. Injections were performed under a constant volume of 0.2 mL.
FG002	Dysport 10 U/Injection Site	Participants received a single dose of Dysport 10 U intradermal injection per injection point (maximum of 10 injection points) on Day 1. The maximal total dose was 100 U. Injections were performed under a constant volume of 0.2 mL.
FG003	Dysport 20 U/Injection Site	Participants received a single dose of Dysport 20 U intradermal injection per injection point (maximum of 10 injection points) on Day 1. The maximal total dose was 200 U. Injections were performed under a constant volume of 0.2 mL.

ID	Title	Description
BG000	Placebo	Participants received a single dose of placebo (matching with Dysport) intradermal injection per injection point (maximum of 10 injection points) on Day 1. Injections were performed under a constant volume of 0.2 mL.
BG001	Dysport 2.5 U/Injection Site

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Time to Onset of Effect in the Spontaneous Numerical Rating Scale (NRS) Score	The time to onset of effect was defined as the time to a decrease from baseline of two points or greater in the spontaneous NRS score. Pain intensity was scored using an 11-point NRS score ranging from 0 to 10, where 0= no pain and 10= worst possible pain. Participants were provided with an Actiwatch® during an Actiwatch® training visit to record their spontaneous NRS scores at home. The Actiwatch® alerted the participants twice a day to record their average and maximal NRS scores over the preceding 12 hours. The questions were asked of the participants by the Actiwatch®: "Please rate your pain by selecting the one number that best describes your pain on average during the last 12 hours." and "Please rate your pain by selecting the one number that best describes your pain at its worst during the last 12 hours." Only descriptive statistical analysis was performed for this outcome measure.	Randomised population included all participants randomised in the double-blind period (Part B). Only participants who reached the time to onset were analysed.	Posted		Mean	Standard Deviation	days		Part B: From baseline (defined as mean of all predose data from Day -7 and including predose on Day 1) up to end of study (Week 16) or early discontinuation.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received a single dose of placebo (matching with Dysport) intradermal injection per injection point (maximum of 10 injection points) on Day 1. Injections were performed under a constant volume of 0.2 mL.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Pancreatogenous diabetes	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment

Title	Organization	Phone	Extension	Email
Medical Director	Ipsen Innovation SAS	see email		clinical.trials@ipsen.com

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 4, 2018	Oct 22, 2020	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Nov 28, 2019	Oct 22, 2020	SAP_001.pdf

ID	Term
D008012	Lidocaine
D019274	Botulinum Toxins, Type A
C542869	abobotulinumtoxinA
D000077330	Saline Solution

ID	Term
D000083	Acetanilides
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814

ID	Title	Description
OG000	Placebo	Participants received a single dose of placebo (matching with Dysport) intradermal injection per injection point (maximum of 10 injection points) on Day 1. Injections were performed under a constant volume of 0.2 mL.
OG001	Dysport 2.5 U/Injection Site	Participants received a single dose of Dysport 2.5 U intradermal injection per injection point (maximum of 10 injection points) on Day 1. The maximal total dose was 25 U. Injections were performed under a constant volume of 0.2 mL.
OG002	Dysport 10 U/Injection Site	Participants received a single dose of Dysport 10 U intradermal injection per injection point (maximum of 10 injection points) on Day 1. The maximal total dose was 100 U. Injections were performed under a constant volume of 0.2 mL.
OG003	Dysport 20 U/Injection Site	Participants received a single dose of Dysport 20 U intradermal injection per injection point (maximum of 10 injection points) on Day 1. The maximal total dose was 200 U. Injections were performed under a constant volume of 0.2 mL.