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Oral LAT8881 in Neuropathic Pain

Primary Purpose

Neuropathic Pain, Diabetic Peripheral Neuropathy (DPN), Post Herpetic Neuralgia (PHN)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LAT8881
Placebo
Sponsored by
Lateral Pharma Pty Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuropathic Pain

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Paratus Clinical Research Kanwal
  • Paratus Clinical Research Blacktown
  • AusTrials
  • Emeritus Research Services
  • University of Bristol
  • Queen Elizabeth University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

LAT8881

Placebo

Arm Description

1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the four-week treatment period.

1 x 30 mg capsule of placebo, taken by mouth, twice daily (morning and evening) during the four-week treatment period.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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..
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.
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.
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.
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.
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.
Rescue Medication Use
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
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)
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)
AUC0-inf after the first dose of IMP and after 4 weeks of treatment

Full Information

First Posted
March 2, 2019
Last Updated
May 20, 2021
Sponsor
Lateral Pharma Pty Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT03865953
Brief Title
Oral LAT8881 in Neuropathic Pain
Official Title
A Phase IIa Study of the Efficacy and Safety of Oral LAT8881 in Neuropathic Pain
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
April 9, 2019 (Actual)
Primary Completion Date
April 19, 2020 (Actual)
Study Completion Date
May 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lateral Pharma Pty Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuropathic Pain, Diabetic Peripheral Neuropathy (DPN), Post Herpetic Neuralgia (PHN)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LAT8881
Arm Type
Active Comparator
Arm Description
1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the four-week treatment period.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
1 x 30 mg capsule of placebo, taken by mouth, twice daily (morning and evening) during the four-week treatment period.
Intervention Type
Drug
Intervention Name(s)
LAT8881
Intervention Description
LAT8881 oral capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo oral capsule
Primary Outcome Measure Information:
Title
Absolute Change in Mean Pain Score, Using an 11 Point Numeric Pain Rating Scale (NPRS)
Description
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
Secondary Outcome Measure Information:
Title
Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo
Description
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
Title
Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS
Description
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
Title
30% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale.
Description
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
Title
50% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale.
Description
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
Title
Maximum Change in Mean NPRS
Description
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
Title
Change in Functioning as Assessed by the Brief Pain Inventory Interference Scale (BPI)
Description
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
Title
Change in Pain Characteristics and Intensity, as Assessed by the Short Form McGill Pain Questionnaire (SF-MPQ-2)
Description
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
Title
Change in Neuropathic Pain Symptoms, as Assessed by Neuropathic Pain Symptom Inventory (NPSI)
Description
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
Title
Change in Emotional Functioning, as Assessed by the Beck Depression Inventory-II
Description
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
Title
Patient Global Impression of Change Score
Description
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
Title
Rescue Medication Use
Description
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
Title
Maximum Plasma Concentration of LAT8881 (Cmax) After Oral LAT8881
Description
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
Title
Time to Maximum Plasma Concentration of LAT8881 (Tmax)
Description
Tmax after the first dose of investigational medicinal product (IMP) and after 4 weeks treatment with IMP
Time Frame
Day 1 and day 28
Title
Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf)
Description
AUC0-inf after the first dose of IMP and after 4 weeks of treatment
Time Frame
Day 1 and Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: symmetrical, bilateral pain in the lower extremities for at least 3 months and 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 no change in diabetic medication planned for the duration of the study Positive sensory symptoms (mechanical or thermal) associated with neuropathic pain, confirmed by: painDETECT questionnaire (PD-Q) and 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: Presence of moderate to severe pain from other causes that may confound assessment or self-evaluation of NP. Subjects with both DPN and PHN
Facility Information:
Facility Name
Paratus Clinical Research Kanwal
City
Kanwal
State/Province
New South Wales
ZIP/Postal Code
2259
Country
Australia
Facility Name
Paratus Clinical Research Blacktown
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Facility Name
AusTrials
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4075
Country
Australia
Facility Name
Emeritus Research Services
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3124
Country
Australia
Facility Name
University of Bristol
City
Bristol
ZIP/Postal Code
BS8 1TD
Country
United Kingdom
Facility Name
Queen Elizabeth University Hospital
City
Glasgow
ZIP/Postal Code
G121 3UW
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
This is an Early Proof of Concept study

Learn more about this trial

Oral LAT8881 in Neuropathic Pain

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