Clinical Trial Results:
A Phase IIa study of the efficacy and safety of oral LAT8881 in neuropathic pain
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Summary
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EudraCT number |
2018-004534-15 |
Trial protocol |
GB |
Global end of trial date |
04 May 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Jun 2021
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First version publication date |
20 Jun 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LAT-NP-001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03865953 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Lateral Pharma Pty Ltd
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Sponsor organisation address |
Level 14, 114 William Street, MELBOURNE, Australia, 3000
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Public contact |
Research & Clinical Trials, Lateral Pharma Pty Ltd, info@lateral-pharma.com
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Scientific contact |
Research & Clinical Trials, Lateral Pharma Pty Ltd, info@lateral-pharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Jul 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 May 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
04 May 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy (whether the drug works) of oral LAT8881 in neuropathic pain compared with placebo, when assessed by change in mean pain intensity scores from baseline to the end of four weeks treatment, based on an 11 point numeric pain rating scale (NPRS).
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Protection of trial subjects |
This study was conducted in compliance with the study protocol, the requirements and obligations of the International Conference on Harmonisation (ICH) and Good Clinical Practice (GCP) guidelines, Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2), the World Medical Association Declaration of Helsinki and its amendments and all applicable local guidelines, laws and
regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Mar 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 12
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Country: Number of subjects enrolled |
Australia: 41
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Worldwide total number of subjects |
53
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
31
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From 65 to 84 years |
22
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 8 sites in total, including Australia (6 sites) and the United Kingdom (2 sites). Enrolment commenced in March 2019 and concluded in February 2020. | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
One hundred and eight (108) subjects signed consent and underwent screening procedures, Fifty-three (53) subjects were eligible and randomized, 25 to LAT8881 then placebo (Group 1) and 28 to placebo then LAT8881 (Group 2) treatment groups. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | ||||||||||||||||||||||||
Blinding implementation details |
Only the staff involved in the generation of the randomisation schedule and labelling of clinical trial supplies had access to the randomisation code during study conduct
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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LAT8881 then Placebo | ||||||||||||||||||||||||
Arm description |
Following a first baseline assessment of 7 days, 1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the four-week treatment period. After washout of 14 days, followed by a second baseline of 7 days, matching placebo 1 x 30 mg capsule taken by mouth, twice daily (morning and evening) during the second four-week treatment period. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
LAT8881
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
one LAT8881 capsule taken in the morning and one LAT8881 capsule taken in the evening
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
one placebo capsule taken in the morning and one placebo capsule taken in the evening
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Arm title
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Placebo then LAT8881 | ||||||||||||||||||||||||
Arm description |
Following a seven day initial baseline, matching placebo (containing excipients only) 1 x 30 mg capsule, taken by mouth, twice daily (morning and evening) during the four-week treatment period. After washout of 14 days, followed by a second baseline of seven days, 1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the second four-week treatment period. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
LAT8881
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
one LAT8881 capsule taken in the morning and one LAT8881 capsule taken in the evening
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
one placebo capsule taken in the morning and one placebo capsule taken in the evening
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
LAT8881 then Placebo
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Reporting group description |
Following a first baseline assessment of 7 days, 1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the four-week treatment period. After washout of 14 days, followed by a second baseline of 7 days, matching placebo 1 x 30 mg capsule taken by mouth, twice daily (morning and evening) during the second four-week treatment period. | ||
Reporting group title |
Placebo then LAT8881
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Reporting group description |
Following a seven day initial baseline, matching placebo (containing excipients only) 1 x 30 mg capsule, taken by mouth, twice daily (morning and evening) during the four-week treatment period. After washout of 14 days, followed by a second baseline of seven days, 1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the second four-week treatment period. | ||
Subject analysis set title |
LAT8881
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
A per-protocol (PP) population was based on duration of investigational medical product (IMP) treatment and protocol deviations. This population excluded subjects with inadequate exposure to IMP or who had other major protocol deviations. Rules for this population were included in the SAP. The PP population was the primary population to analyse efficacy endpoints. Demographic and baseline characteristics of the PP population were also be presented.
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Subject analysis set title |
Placebo
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
A per-protocol (PP) population was based on duration of investigational medical product (IMP) treatment and protocol deviations. This population excluded subjects with inadequate exposure to IMP or who had other major protocol deviations. Rules for this population were included in the SAP. The PP population was the primary population to analyse efficacy endpoints. Demographic and baseline characteristics of the PP population were also be presented.
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End point title |
Absolute change in mean pain score | ||||||||||||
End point 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.
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End point type |
Primary
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End point timeframe |
from baseline to the last week of each treatment period (Week 4)
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| Notes [1] - 23 subjects completed the LAT-8881 to Placebo arm of the study. [2] - 25 subjects completed the Placebo-LAT8881 arm of the study |
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Statistical analysis title |
Absolute Change in Mean Pain Score | ||||||||||||
Statistical analysis description |
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 significance
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Comparison groups |
LAT8881 v Placebo
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Number of subjects included in analysis |
48
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | ||||||||||||
P-value |
= 0.67 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.14
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.76 | ||||||||||||
upper limit |
0.49 | ||||||||||||
| Notes [3] - Analysis used a two-period two-treatment crossover design, with 23 subjects completing the LAT8881-Placebo arm and 25 subjects the Placebo-LAT8881 arm, therefore 48 subjects in total were analysed. |
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End point title |
Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo | ||||||||||||||||||||||||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose, 0.5,1,2,4 and 6 hours after the first and last dose of LAT8881 and placebo
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS | |||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
1,2 and 3 weeks
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
30% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale. | |||||||||
End point 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 larger negative number represents a greater reduction in pain.
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End point type |
Secondary
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End point timeframe |
4 weeks
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| No statistical analyses for this end point | ||||||||||
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End point title |
50% Responder Rate in Oral LAT8881 Compared With Placebo | |||||||||
End point 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 larger negative number represents a greater reduction in pain.
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End point type |
Secondary
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End point timeframe |
4 weeks
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| No statistical analyses for this end point | ||||||||||
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End point title |
Maximum Change in Mean NPRS | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
During the 4 week treatment period
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Functioning as Assessed by the Brief Pain Inventory Interference Scale (BPI) | ||||||||||||
End point 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". A reduction in mean score indicates a decrease in interference
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End point type |
Secondary
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End point timeframe |
4 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Pain Characteristics and Intensity, as Assessed by the Short Form McGill Pain Questionnaire (SF-MPQ-2) | ||||||||||||
End point 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). A larger negative number represents
a greater reduction in pain.
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End point type |
Secondary
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End point timeframe |
4 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Neuropathic Pain Symptoms, as Assessed by Neuropathic Pain Symptom Inventory (NPSI) | ||||||||||||
End point 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. A higher score indicates a higher pain intensity.
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End point type |
Secondary
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End point timeframe |
4 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Emotional Functioning, as Assessed by the Beck Depression Inventory-II | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
4 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Patient Global Impression of Change Score | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
4 weeks
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were collected from the first dose of study treatment until the End of Study visit, maximum 93
days
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||
Dictionary version |
22.0
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Reporting groups
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Reporting group title |
LAT8881
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Reporting group description |
1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the four-week treatment period | |||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
1 x 30 mg capsule of placebo, taken by mouth, twice daily (morning and evening) during the four-week treatment period | |||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
