Oral LAT8881 in Neuropathic Pain

A Phase IIa Study of 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.

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain; Diabetic Peripheral Neuropathy (DPN); Post Herpetic Neuralgia (PHN)
• Intervention / Treatment: Drug: Placebo; Drug: LAT8881

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.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kanwal, New South Wales, Australia, 2259
      • Paratus Clinical Research Kanwal
    • Sydney, New South Wales, Australia, 2148
      • Paratus Clinical Research Blacktown
  • Queensland
    • Brisbane, Queensland, Australia, 4075
      • Austrials
  • Victoria
    • Melbourne, Victoria, Australia, 3124
      • Emeritus Research Services
• United Kingdom
  • Bristol, United Kingdom, BS8 1TD
    • University of Bristol
  • Glasgow, United Kingdom, G121 3UW
    • Queen Elizabeth University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: LAT8881; 1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the four-week treatment period.	Drug: LAT8881; LAT8881 oral capsule
Placebo Comparator: Placebo; 1 x 30 mg capsule of placebo, taken by mouth, twice daily (morning and evening) during the four-week treatment period.	Drug: Placebo; Placebo oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Lateral Pharma Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2019
• Primary Completion (Actual): April 19, 2020
• Study Completion (Actual): May 3, 2020

Study Registration Dates

• First Submitted: March 2, 2019
• First Submitted That Met QC Criteria: March 6, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: May 20, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Neuralgia; Peripheral Nervous System Diseases; Neuralgia, Postherpetic
• Other Study ID Numbers: LAT-NP-001; 2018-004534-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is an Early Proof of Concept study

Drug and device information, study documents

• 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