This is a randomised, placebo-controlled, double-blind, crossover, phase IIa study to investigate the efficacy and safety of oral LAT8881 in neuropathic pain.
This is a randomised, placebo-controlled, double-blind, crossover, phase IIa study to investigate the efficacy and safety of oral LAT8881 in neuropathic pain. After a one week baseline period, subjects entered into the study will be randomised to receive Investigational Medicinal Product (IMP) (LAT8881 or placebo) twice daily for four weeks. The first treatment period will be followed by a washout period of two weeks and then a second baseline period of one week. Subjects will not take any IMP over these three weeks. After the second baseline period, subjects will cross over to receive the second treatment (either LAT8881 or placebo, whichever treatment was not received in the first treatment period) twice daily for four weeks. The pharmacokinetics (PK) of LAT8881 will be investigated in 15 subjects (PK subjects) at selected Australian sites.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
53
Paratus Clinical Research Kanwal
Kanwal, New South Wales, Australia
Paratus Clinical Research Blacktown
Sydney, New South Wales, Australia
AusTrials
Brisbane, Queensland, Australia
Emeritus Research Services
Melbourne, Victoria, Australia
Absolute Change in Mean Pain Score, Using an 11 Point Numeric Pain Rating Scale (NPRS)
The 11-point numeric pain rating scale (NPRS) ranges from 0 ("no pain") to 10 ("worst pain imaginable"). A larger negative number represents a greater reduction in pain. The efficacy of oral LAT8881 in neuropathic pain was compared with placebo, when assessed by change in mean pain intensity scores, using this 11 point numeric pain rating scale.
Time frame: Baseline to Week 4
Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo
To investigate the effect of oral LAT8881 in neuropathic pain compared with placebo, as measured by the numeric pain rating score (NPRS). The 11-point numeric pain rating scale ranges from 0 ("no pain") to 10 ("worst pain imaginable"). A larger negative number represents a greater reduction in pain. This outcome was investigated only in the pharmacokinetic subset of per protocol subjects.
Time frame: Pre-dose, 0.5,1,2,4 and 6 hours after the first and last dose of LAT8881 and placebo
Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS
To investigate the effect of oral LAT8881 on mean pain scores in neuropathic pain compared with placebo, as measured by the numeric pain rating scale (NPRS). The 11-point numeric pain rating scale ranges from 0 ("no pain") to 10 ("worst pain imaginable"). A larger negative number represents a greater reduction in pain.
Time frame: 1,2 and 3 weeks
30% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale.
To determine the proportion of subjects with at least a 30% reduction in mean NPRS after 4 weeks treatment. The 11-point numeric pain rating scale (NPRS) ranges from 0 ("no pain") to 10 ("worst pain imaginable"). A decrease in pain score represents an improvement in pain.
Time frame: 4 weeks
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University of Bristol
Bristol, United Kingdom
Queen Elizabeth University Hospital
Glasgow, United Kingdom
50% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale.
To determine the proportion of subjects with at least a 50% reduction in mean the numeric pain rating scale (NPRS) after 4 weeks treatment. The 11-point numeric pain rating scale ranges from 0 ("no pain") to 10 ("worst pain imaginable"). A decrease in pain score represents an improvement in pain.
Time frame: 4 weeks
Maximum Change in Mean NPRS
To determine the maximum effects of oral LAT8881 in neuropathic pain, compared with placebo, as measured by the numeric pain rating scale (NPRS). The 11-point numeric pain rating scale ranges from 0 ("no pain") to 10 ("worst pain imaginable"). A larger negative number represents a greater reduction in pain..
Time frame: 1,2,3 or 4 weeks
Change in Functioning as Assessed by the Brief Pain Inventory Interference Scale (BPI)
To evaluate the effects of oral LAT8881, compared with placebo, on functioning when measured by the Brief Pain Inventory Interference Scale (BPI). The BPI assesses the severity of pain and its impact on functioning. Patients are asked to assess the level of interference experienced across seven items; general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life, with a "0" meaning "no interference, and a "10", at the top end of the scale, meaning "complete interference". The result is the mean of the score of the seven items. A reduction in mean score indicates a decrease in interference.
Time frame: 4 weeks
Change in Pain Characteristics and Intensity, as Assessed by the Short Form McGill Pain Questionnaire (SF-MPQ-2)
To evaluate the effect of oral LAT8881, compared with placebo, on pain symptoms in subjects with neuropathic pain, when measured by the Short Form McGill Pain Questionnaire (SF-MPQ-2). The SF-MPQ-2 contains 22 descriptors of pain and related symptoms, each scored from "0" (none) to "10" (worst possible). The scores for each descriptor at each visit are averaged to give a mean score from 0 to 10. A larger negative number represents a greater reduction in pain.
Time frame: 4 weeks
Change in Neuropathic Pain Symptoms, as Assessed by Neuropathic Pain Symptom Inventory (NPSI)
The Neuropathic Pain Symptom Inventory (NPSI) contains ten items related to different pain descriptors (e.g. burning, squeezing, electric-shock, stabbing, tingling), allowing the assessment of the different dimensions of neuropathic pain, and two items related to the frequency and duration of pain. Each pain descriptor is rated on an 11-point numeric rating scale from 0 (no pain) to 10 (worst imaginable pain). Total pain intensity score is calculated by the sum of the 10 descriptors and can range from 0 to 100. A higher score indicates a higher pain intensity. A larger negative number represents a greater reduction in pain.
Time frame: 4 weeks
Change in Emotional Functioning, as Assessed by the Beck Depression Inventory-II
To evaluate the effect of oral LAT8881, compared with placebo, on emotional functioning when measured by the Beck Depression Inventory-II (BDI-II). The BDI-II consists of 21 items; each item is a list of four statements arranged in order of increasing severity about a particular symptom of depression. Each statement is scored from 0 to 3. Each of the 21 items is summed to give a single score for the BDI-II. Scores can range from 0 (no depression) to 63 (severe depression). An increase from baseline to the end of treatment indicates a deterioration.
Time frame: 4 weeks
Patient Global Impression of Change Score
The Patient Global Impression of Change (PGIC) is a a single-item rating by subjects of their improvement with treatment during a clinical trial. It asks the subject to rate their improvement with therapy on a 7-point scale, ranging from substantially worse ("0") to substantially improved ("7"), with no change ("4") as the mid-point. A score above 4 indicates an improvement.
Time frame: 4 weeks
Rescue Medication Use
To determine the change from baseline in paracetamol rescue medication use during oral LAT8881 administration, compared with placebo.
Time frame: Weekly over four-week treatment
Maximum Plasma Concentration of LAT8881 (Cmax) After Oral LAT8881
Cmax is calculated after the first dose of IMP on Day 1 and after 4 weeks treatment on the morning of Day 28
Time frame: Day 1 and Day 28
Time to Maximum Plasma Concentration of LAT8881 (Tmax)
Tmax after the first dose of investigational medicinal product (IMP) and after 4 weeks treatment with IMP
Time frame: Day 1 and day 28
Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf)
AUC0-inf after the first dose of IMP and after 4 weeks of treatment
Time frame: Day 1 and Day 28