A Double-blind, Randomised, Placebo Controlled, Proof-of-concept Study in Subjects With Abdominal or Thoracic Chronic Scar Pain to Assess the Analgesic Properties of Intradermal Doses of Dysport®
Overview
- Phase
- Phase 2
- Intervention
- Lidocaine
- Conditions
- Chronic Scar Pain
- Sponsor
- Ipsen
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Time to Onset of Effect in the Spontaneous Numerical Rating Scale (NRS) Score
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Investigators
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.
Arms & Interventions
Pre-Randomization, Run-In period (part A)
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).
Intervention: Lidocaine
Pre-Randomization, Run-In period (part A)
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).
Intervention: Placebo
Dysport dose 1 (part B)
Dysport dose 1 as a single-dose, intradermal injection.
Intervention: Botulinum toxin type A
Dysport dose 2 (part B)
Dysport dose 2 as a single-dose, intradermal injection.
Intervention: Botulinum toxin type A
Dysport dose 3 (part B)
Dysport dose 3 as a single-dose, intradermal injection.
Intervention: Botulinum toxin type A
Placebo (saline solution) (part B)
Placebo single-dose, intradermal injection.
Intervention: Placebo
Outcomes
Primary Outcomes
Time to Onset of Effect in the Spontaneous Numerical Rating Scale (NRS) Score
Time Frame: 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.
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.
Time to Peak Effect in the Spontaneous NRS Score
Time Frame: 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.
The time to peak effect was defined as the time to reach the peak effect 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."
Peak Effect in the Spontaneous NRS Score
Time Frame: 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.
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.
Duration of Effect in the Spontaneous NRS Score
Time Frame: 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.
The duration of effect was defined as the duration between time to onset and last timepoint for which decrease from baseline in the spontaneous NRS score was two points or greater. 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."
Secondary Outcomes
- Change From Baseline in the Spontaneous NRS Score Throughout the Study(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.)
- Change From Baseline in the Stimulus-Evoked NRS Score on the Painful Area at Weeks 6 and 12(Part B: Baseline (defined as mean of all predose data from Day -7 and including predose on Day 1) and Weeks 6 and 12)