Diabetic Peripheral Neuropathy (DPN), Neuropathic Pain, Post Herpetic Neuralgia (PHN)
Conditions
Brief summary
This is a randomised, placebo-controlled, double-blind, crossover, phase IIa study to investigate the efficacy and safety of oral LAT8881 in neuropathic pain.
Detailed description
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.
Interventions
DRUGLAT8881
LAT8881 oral capsule
DRUGPlacebo
Placebo oral capsule
Sponsors
Lateral Pharma Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is the first study with LAT8881 in subjects with neuropathic pain. As such, it has been designed to evaluate, in a well-defined patient group, the concept that LAT8881 is safe and effective in this indication. Subjects enrolled into this study have been diagnosed with Post Herpetic Neuralgia (PHN) or Diabetic Peripheral Neuropathy (DPN), both conditions being well accepted examples of neuropathic pain. Because the pain is chronic, without a period effect, and treatment is symptomatic rather than curative, a crossover study is considered appropriate. Studies with other agents have successfully demonstrated analgesic effects in PHN and DPN with a crossover study design
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of post herpetic neuralgia, with pain persisting for at least 3 months after the onset of herpes zoster rash OR 2. Clinical diagnosis of distal painful polyneuropathy due to Type I or Type II diabetes mellitus with: 1. symmetrical, bilateral pain in the lower extremities for at least 3 months and 2. diabetes under control for at least 3 months prior to randomisation, as indicated by a glycated haemoglobin level (HbA1c) of ≤ 11% (97 mmol/mol) and on a stable dose of insulin or oral diabetic medication for 3 months prior to screening, and 3. no change in diabetic medication planned for the duration of the study 3. Positive sensory symptoms (mechanical or thermal) associated with neuropathic pain, confirmed by: 1. painDETECT questionnaire (PD-Q) and 2. Clinical assessment, showing signs of neuropathic pain in either a dermatomal (PHN) or distal symmetrical distribution (DPN) 8\. An average daily pain score on the numeric pain rating scale (NPRS) of at least 4 and no more than 8 in the last five diary entries before randomisation
Exclusion criteria
1. Presence of moderate to severe pain from other causes that may confound assessment or self-evaluation of NP. 2. Subjects with both DPN and PHN
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Mean Pain Score, Using an 11 Point Numeric Pain Rating Scale (NPRS) | Baseline to Week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | 1,2 and 3 weeks | 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. |
| 30% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale. | 4 weeks | 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. |
| 50% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale. | 4 weeks | 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. |
| Maximum Change in Mean NPRS | 1,2,3 or 4 weeks | 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.. |
| Change in Functioning as Assessed by the Brief Pain Inventory Interference Scale (BPI) | 4 weeks | 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. |
| Change in Pain Characteristics and Intensity, as Assessed by the Short Form McGill Pain Questionnaire (SF-MPQ-2) | 4 weeks | 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. |
| Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Pre-dose, 0.5,1,2,4 and 6 hours 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. |
| Change in Emotional Functioning, as Assessed by the Beck Depression Inventory-II | 4 weeks | 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. |
| Patient Global Impression of Change Score | 4 weeks | 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. |
| Rescue Medication Use | Weekly over four-week treatment | To determine the change from baseline in paracetamol rescue medication use during oral LAT8881 administration, compared with placebo. |
| Maximum Plasma Concentration of LAT8881 (Cmax) After Oral LAT8881 | Day 1 and Day 28 | Cmax is calculated after the first dose of IMP on Day 1 and after 4 weeks treatment on the morning of Day 28 |
| Time to Maximum Plasma Concentration of LAT8881 (Tmax) | Day 1 and day 28 | Tmax after the first dose of investigational medicinal product (IMP) and after 4 weeks treatment with IMP |
| Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) | Day 1 and Day 28 | AUC0-inf after the first dose of IMP and after 4 weeks of treatment |
| Change in Neuropathic Pain Symptoms, as Assessed by Neuropathic Pain Symptom Inventory (NPSI) | 4 weeks | 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. |
Countries
Australia, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LAT8881, Then Placebo In the first intervention period, 1 x 30 mg capsule of LAT8881 was taken twice daily (morning and evening) for four weeks. After a 3 week washout/baseline non-treatment period, a placebo capsule was taken twice daily (morning and evening) for four weeks. | 25 |
| Placebo, Then LAT8881 In the first intervention period, a placebo capsule was taken twice daily (morning and evening) for four weeks. After a 3 week washout/baseline non-treatment period, 1 x 30 mg capsule of LAT8881 was taken twice daily (morning and evening) for four weeks. | 28 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (4 Weeks) | Lost to Follow-up | 2 | 0 |
| First Intervention (4 Weeks) | Protocol Violation | 0 | 1 |
| Second Intervention (4 Weeks) | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | LAT8881, Then Placebo | Placebo, Then LAT8881 | Total |
|---|---|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 11.33 | 58.5 years STANDARD_DEVIATION 8.91 | 59.8 years STANDARD_DEVIATION 10.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 28 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Neuropathic pain history Diabetic peripheral neuropathy (DPN) | 17 Participants | 26 Participants | 43 Participants |
| Neuropathic pain history Post herpetic neuralgia (PHN) | 8 Participants | 2 Participants | 10 Participants |
| PainDETECT questionnaire (PD-Q) scores | 21.0 units on a scale STANDARD_DEVIATION 3.62 | 20.9 units on a scale STANDARD_DEVIATION 5.03 | 20.9 units on a scale STANDARD_DEVIATION 4.38 |
| Region of Enrollment Australia | 19 participants | 22 participants | 41 participants |
| Region of Enrollment United Kingdom | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 15 Participants | 7 Participants | 22 Participants |
| Sex: Female, Male Male | 10 Participants | 21 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 51 |
| other Total, other adverse events | 5 / 51 | 6 / 51 |
| serious Total, serious adverse events | 0 / 51 | 0 / 51 |
Outcome results
Primary
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
Population: The per protocol population was used for all efficacy analyses. This population excluded subjects with inadequate exposure to treatment or who had other major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAT8881 | Absolute Change in Mean Pain Score, Using an 11 Point Numeric Pain Rating Scale (NPRS) | -0.87 score on a scale | Standard Deviation 1.53 |
| Placebo | Absolute Change in Mean Pain Score, Using an 11 Point Numeric Pain Rating Scale (NPRS) | -0.74 score on a scale | Standard Deviation 2.09 |
Comparison: Subject numbers gave a 90% power to demonstrate a statistically significant difference in the mean change from baseline NPRS for the active treatment compared with placebo of at least 1 unit, with a two sided test at a 5% level of significancep-value: 0.6795% CI: [-0.76, 0.49]Mixed Models Analysis
Secondary
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
Population: Per protocol population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LAT8881 | 30% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale. | 20 Participants |
| Placebo | 30% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale. | 19 Participants |
Secondary
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
Population: Per protocol population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LAT8881 | 50% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale. | 6 Participants |
| Placebo | 50% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale. | 9 Participants |
Secondary
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
Population: Subgroup of the pharmacokinetic population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LAT8881 | Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) | AUC0-inf, Day 1 | NA ng-hr/mL |
| LAT8881 | Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) | AUC0-inf, Day 28 | NA ng-hr/mL |
| Placebo | Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) | AUC0-inf, Day 1 | NA ng-hr/mL |
| Placebo | Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) | AUC0-inf, Day 28 | NA ng-hr/mL |
Secondary
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
Population: Per protocol population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAT8881 | Change in Emotional Functioning, as Assessed by the Beck Depression Inventory-II | Baseline BDI-II | 11.3 score on a scale | Standard Deviation 8.6 |
| LAT8881 | Change in Emotional Functioning, as Assessed by the Beck Depression Inventory-II | Change from baseline | -1.1 score on a scale | Standard Deviation 4.14 |
| Placebo | Change in Emotional Functioning, as Assessed by the Beck Depression Inventory-II | Baseline BDI-II | 12.1 score on a scale | Standard Deviation 9.3 |
| Placebo | Change in Emotional Functioning, as Assessed by the Beck Depression Inventory-II | Change from baseline | -1.2 score on a scale | Standard Deviation 7.98 |
Secondary
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
Population: Per protocol population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAT8881 | Change in Functioning as Assessed by the Brief Pain Inventory Interference Scale (BPI) | Baseline BPI | 4.71 score on a scale | Standard Deviation 2.45 |
| LAT8881 | Change in Functioning as Assessed by the Brief Pain Inventory Interference Scale (BPI) | Change from baseline | -0.57 score on a scale | Standard Deviation 1.83 |
| Placebo | Change in Functioning as Assessed by the Brief Pain Inventory Interference Scale (BPI) | Baseline BPI | 4.91 score on a scale | Standard Deviation 2.32 |
| Placebo | Change in Functioning as Assessed by the Brief Pain Inventory Interference Scale (BPI) | Change from baseline | -1.12 score on a scale | Standard Deviation 1.97 |
Secondary
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
Population: Per protocol population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAT8881 | Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | Baseline | 6.18 units on a scale | Standard Deviation 1.53 |
| LAT8881 | Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | Change from baseline at Week 1 | -0.50 units on a scale | Standard Deviation 1.37 |
| LAT8881 | Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | Change from baseline at Week 2 | -0.73 units on a scale | Standard Deviation 1.49 |
| LAT8881 | Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | Change from baseline at Week 3 | -0.84 units on a scale | Standard Deviation 1.61 |
| Placebo | Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | Change from baseline at Week 3 | -0.84 units on a scale | Standard Deviation 1.88 |
| Placebo | Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | Baseline | 6.18 units on a scale | Standard Deviation 1.45 |
| Placebo | Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | Change from baseline at Week 2 | -0.91 units on a scale | Standard Deviation 1.62 |
| Placebo | Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | Change from baseline at Week 1 | -0.55 units on a scale | Standard Deviation 1.27 |
Secondary
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
Population: Per protocol population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAT8881 | Change in Neuropathic Pain Symptoms, as Assessed by Neuropathic Pain Symptom Inventory (NPSI) | Baseline NPSI | 40.7 score on a scale | Standard Deviation 17.2 |
| LAT8881 | Change in Neuropathic Pain Symptoms, as Assessed by Neuropathic Pain Symptom Inventory (NPSI) | Change from baseline | -6.0 score on a scale | Standard Deviation 14.5 |
| Placebo | Change in Neuropathic Pain Symptoms, as Assessed by Neuropathic Pain Symptom Inventory (NPSI) | Baseline NPSI | 41.1 score on a scale | Standard Deviation 16.2 |
| Placebo | Change in Neuropathic Pain Symptoms, as Assessed by Neuropathic Pain Symptom Inventory (NPSI) | Change from baseline | -7.4 score on a scale | Standard Deviation 16.9 |
Secondary
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
Population: Pharmacokinetic subset of the per protocol population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 6 hours after first dose | 0.0 score on a scale | Standard Deviation 0.68 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Absolute baseline score, last dosing day | 4.4 score on a scale | Standard Deviation 2.2 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 0.5 hours after last dose | -0.6 score on a scale | Standard Deviation 2.43 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 1 hour after last dose | -0.5 score on a scale | Standard Deviation 2.58 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 2 hours after last dose | -0.8 score on a scale | Standard Deviation 2.19 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 4 hours after last dose | -0.5 score on a scale | Standard Deviation 2.26 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 6 hours after last dose | -0.7 score on a scale | Standard Deviation 1.93 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Absolute baseline score, first dose | 4.5 score on a scale | Standard Deviation 2.2 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 0.5 hours after first dose | -0.1 score on a scale | Standard Deviation 0.77 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 1 hour after first dose | -0.4 score on a scale | Standard Deviation 0.63 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 2 hours after first dose | -0.1 score on a scale | Standard Deviation 0.95 |
| LAT8881 | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 4 hours after first dose | 0.1 score on a scale | Standard Deviation 1.07 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 2 hours after first dose | -0.8 score on a scale | Standard Deviation 2.26 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 6 hours after first dose | -0.7 score on a scale | Standard Deviation 1.77 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 6 hours after last dose | -0.4 score on a scale | Standard Deviation 0.84 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Absolute baseline score, last dosing day | 4.0 score on a scale | Standard Deviation 2.2 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 1 hour after first dose | -0.6 score on a scale | Standard Deviation 1.95 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 0.5 hours after last dose | -0.4 score on a scale | Standard Deviation 0.84 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Absolute baseline score, first dose | 4.8 score on a scale | Standard Deviation 1.9 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 1 hour after last dose | -0.4 score on a scale | Standard Deviation 1.02 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 4 hours after first dose | -0.6 score on a scale | Standard Deviation 2.17 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 2 hours after last dose | -0.1 score on a scale | Standard Deviation 0.77 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 0.5 hours after first dose | -0.2 score on a scale | Standard Deviation 1.53 |
| Placebo | Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | Change from baseline, 4 hours after last dose | -0.4 score on a scale | Standard Deviation 0.93 |
Secondary
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
Population: Per protocol population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAT8881 | Change in Pain Characteristics and Intensity, as Assessed by the Short Form McGill Pain Questionnaire (SF-MPQ-2) | Baseline SF-MPQ-2 | 3.88 score on a scale | Standard Deviation 1.81 |
| LAT8881 | Change in Pain Characteristics and Intensity, as Assessed by the Short Form McGill Pain Questionnaire (SF-MPQ-2) | Change from baseline | -0.66 score on a scale | Standard Deviation 1.34 |
| Placebo | Change in Pain Characteristics and Intensity, as Assessed by the Short Form McGill Pain Questionnaire (SF-MPQ-2) | Baseline SF-MPQ-2 | 3.86 score on a scale | Standard Deviation 1.73 |
| Placebo | Change in Pain Characteristics and Intensity, as Assessed by the Short Form McGill Pain Questionnaire (SF-MPQ-2) | Change from baseline | -0.63 score on a scale | Standard Deviation 1.7 |
Secondary
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
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAT8881 | Maximum Change in Mean NPRS | -1.53 score on a scale | Standard Deviation 1.37 |
| Placebo | Maximum Change in Mean NPRS | -1.55 score on a scale | Standard Deviation 1.41 |
Secondary
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
Population: Subgroup of the pharmacokinetic population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LAT8881 | Maximum Plasma Concentration of LAT8881 (Cmax) After Oral LAT8881 | Cmax, Day 1 | NA ng/mL |
| LAT8881 | Maximum Plasma Concentration of LAT8881 (Cmax) After Oral LAT8881 | Cmax, Day 28 | NA ng/mL |
| Placebo | Maximum Plasma Concentration of LAT8881 (Cmax) After Oral LAT8881 | Cmax, Day 1 | NA ng/mL |
| Placebo | Maximum Plasma Concentration of LAT8881 (Cmax) After Oral LAT8881 | Cmax, Day 28 | NA ng/mL |
Secondary
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
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAT8881 | Patient Global Impression of Change Score | 4.5 score on a scale | Standard Deviation 1.23 |
| Placebo | Patient Global Impression of Change Score | 4.8 score on a scale | Standard Deviation 1.33 |
Secondary
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
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LAT8881 | Rescue Medication Use | Week 1 | NA gram |
| LAT8881 | Rescue Medication Use | Week 2 | NA gram |
| LAT8881 | Rescue Medication Use | Week 3 | NA gram |
| LAT8881 | Rescue Medication Use | Week 4 | NA gram |
| Placebo | Rescue Medication Use | Week 4 | NA gram |
| Placebo | Rescue Medication Use | Week 1 | NA gram |
| Placebo | Rescue Medication Use | Week 3 | NA gram |
| Placebo | Rescue Medication Use | Week 2 | NA gram |
Secondary
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
Population: subgroup of the pharmacokinetic population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LAT8881 | Time to Maximum Plasma Concentration of LAT8881 (Tmax) | Tmax, Day 28 | NA hours |
| LAT8881 | Time to Maximum Plasma Concentration of LAT8881 (Tmax) | Tmax, Day 1 | NA hours |
| Placebo | Time to Maximum Plasma Concentration of LAT8881 (Tmax) | Tmax, Day 1 | NA hours |
| Placebo | Time to Maximum Plasma Concentration of LAT8881 (Tmax) | Tmax, Day 28 | NA hours |