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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-004534-15 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LAT8881 | Active Comparator | 1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the four-week treatment period. |
|
| Placebo | Placebo Comparator | 1 x 30 mg capsule of placebo, taken by mouth, twice daily (morning and evening) during the four-week treatment period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LAT8881 | Drug | LAT8881 oral capsule |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Clinical diagnosis of post herpetic neuralgia, with pain persisting for at least 3 months after the onset of herpes zoster rash OR
Clinical diagnosis of distal painful polyneuropathy due to Type I or Type II diabetes mellitus with:
Positive sensory symptoms (mechanical or thermal) associated with neuropathic pain, confirmed by:
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Paratus Clinical Research Kanwal | Kanwal | New South Wales | 2259 | Australia | ||
| Paratus Clinical Research Blacktown |
This is an Early Proof of Concept study
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (4 Weeks) |
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| |||||||||||||||||||||
| Washout/Baseline Period (3 Weeks) |
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| Second Intervention (4 Weeks) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Placebo, Then LAT8881 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 4 |
|
Adverse events were collected from the first dose of study treatment until the End of Study visit, maximum 93 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LAT8881 | 1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the four-week treatment period. LAT8881: LAT8881 oral capsule |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA version 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mr David Kenley | Lateral Pharma Pty Ltd | +61 (0)400 151 490 | dk@lateral-pharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 9, 2019 | Mar 3, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 27, 2020 | Mar 3, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009437 | Neuralgia |
| D051474 | Neuralgia, Postherpetic |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D010146 | Pain |
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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
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| Drug |
Placebo oral capsule |
|
| 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. | 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. | 4 weeks |
| 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. | 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.. | 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. | 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. | 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. | 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. | 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. | 4 weeks |
| Rescue Medication Use | To determine the change from baseline in paracetamol rescue medication use during oral LAT8881 administration, compared with placebo. | 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 | 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 | 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 | Day 1 and Day 28 |
| Sydney |
| New South Wales |
| 2148 |
| Australia |
| AusTrials | Brisbane | Queensland | 4075 | Australia |
| Emeritus Research Services | Melbourne | Victoria | 3124 | Australia |
| University of Bristol | Bristol | BS8 1TD | United Kingdom |
| Queen Elizabeth University Hospital | Glasgow | G121 3UW | United Kingdom |
| NOT COMPLETED |
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| NOT COMPLETED |
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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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Neuropathic pain history | Count of Participants | Participants |
|
| PainDETECT questionnaire (PD-Q) scores | The painDETECT questionnaire (PD-Q) is used to assist in identifying patients with neuropathic pain. It consists of seven pain sensory symptom items which are scored from 0 "not at all" to 5 "very strongly" plus one pain course pattern item scored from -1 to 2 and and one pain radiation item scored as 2 or 0. From this questionnaire, a PD-Q total score, ranging from -1 to 38 is calculated. A total score ≥19 indicates a neuropathic component is likely, ≤12 indicates a neuropathic component is unlikely and scores 13-18 are considered uncertain. | Mean | Standard Deviation | units on a scale |
|
| OG001 | Placebo | 1 x 30 mg capsule of placebo, taken by mouth, twice daily (morning and evening) during the four-week treatment period. Placebo: Placebo oral capsule |
|
|
|
| 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. | Pharmacokinetic subset of the per protocol population | Posted | Mean | Standard Deviation | score on a scale | Pre-dose, 0.5,1,2,4 and 6 hours after the first and last dose of LAT8881 and placebo |
|
|
|
| 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. | Per protocol population | Posted | Mean | Standard Deviation | units on a scale | 1,2 and 3 weeks |
|
|
|
| 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. | Per protocol population | Posted | Count of Participants | Participants | No | 4 weeks |
|
|
|
| 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. | Per protocol population | Posted | Count of Participants | Participants | No | 4 weeks |
|
|
|
| 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.. | Per protocol population | Posted | Mean | Standard Deviation | score on a scale | 1,2,3 or 4 weeks |
|
|
|
| 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. | Per protocol population. | Posted | Mean | Standard Deviation | score on a scale | 4 weeks |
|
|
|
| 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. | Per protocol population. | Posted | Mean | Standard Deviation | score on a scale | 4 weeks |
|
|
|
| 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. | Per protocol population. | Posted | Mean | Standard Deviation | score on a scale | 4 weeks |
|
|
|
| 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. | Per protocol population. | Posted | Mean | Standard Deviation | score on a scale | 4 weeks |
|
|
|
| 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. | Per protocol population | Posted | Mean | Standard Deviation | score on a scale | 4 weeks |
|
|
|
| Secondary | Rescue Medication Use | To determine the change from baseline in paracetamol rescue medication use during oral LAT8881 administration, compared with placebo. | Full analysis set | Posted | Mean | Standard Deviation | gram | Weekly over four-week treatment |
|
|
|
| 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 | Subgroup of the pharmacokinetic population | Posted | Mean | Standard Deviation | ng/mL | Day 1 and Day 28 |
|
|
|
| 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 | subgroup of the pharmacokinetic population | Posted | Mean | Standard Deviation | hours | Day 1 and day 28 |
|
|
|
| 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 | Subgroup of the pharmacokinetic population | Posted | Mean | Standard Deviation | ng-hr/mL | Day 1 and Day 28 |
|
|
|
| 0 |
| 51 |
| 0 |
| 51 |
| 5 |
| 51 |
| EG001 | Placebo | 1 x 30 mg capsule of placebo, taken by mouth, twice daily (morning and evening) during the four-week treatment period. Placebo: Placebo oral capsule | 0 | 51 | 0 | 51 | 6 | 51 |
| Headache | Nervous system disorders | MedDRA version 22.0 | Systematic Assessment |
|
Except for legal reasons, the investigator will not reveal the result of the study to a third party without a mutual agreement about the analysis and interpretation of the data with the sponsor.
| D009461 |
| Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Change from baseline, 1 hour after first dose |
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| Change from baseline, 2 hours after first dose |
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| Change from baseline, 4 hours after first dose |
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| Change from baseline, 6 hours after first dose |
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| Absolute baseline score, last dosing day |
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| Change from baseline, 0.5 hours after last dose |
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| Change from baseline, 1 hour after last dose |
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| Change from baseline, 2 hours after last dose |
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| Change from baseline, 4 hours after last dose |
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| Change from baseline, 6 hours after last dose |
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| Change from baseline at Week 2 |
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| Change from baseline at Week 3 |
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| Week 3 |
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| Week 4 |
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