Neuropathic PainPhase 2NCT03865953
Oral LAT8881 in Neuropathic Pain
A Phase 2 study testing LAT8881 in people with Neuropathic Pain and Diabetic Peripheral Neuropathy (DPN), run by Lateral Pharma Pty Ltd at 6 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Neuropathic Pain, Diabetic Peripheral Neuropathy (DPN), Post Herpetic Neuralgia (PHN)
- What is being tested?
- LAT8881
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 9 Apr 2019to 3 May 2020
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- Presence of moderate to severe pain from other causes that may confound assessment or self-evaluation of NP.
- Subjects with both DPN and PHN
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Australia4 sites
AusTrials
Brisbane, Queensland, 4075
Paratus Clinical Research Kanwal
Kanwal, New South Wales, 2259
Emeritus Research Services
Melbourne, Victoria, 3124
Paratus Clinical Research Blacktown
Sydney, New South Wales, 2148
United Kingdom2 sites
University of Bristol
Bristol, BS8 1TD
Queen Elizabeth University Hospital
Glasgow, G121 3UW
About this study
Official title: 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.
Read the 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.
- Being tested
- LAT8881, Placebo
- Medical subject headings
- Neuralgia, Neuralgia, Postherpetic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAT8881Drug
LAT8881 oral capsule
PlaceboDrug
Placebo oral capsule
| Study group | Role | What they receive |
|---|---|---|
| LAT8881 | Active comparator | 1 x 30 mg capsule of LAT8881 taken by mouth, twice daily (morning and evening) during the four-week treatment period. Receives: Drug: LAT8881 |
| Placebo | Placebo comparator | 1 x 30 mg capsule of placebo, taken by mouth, twice daily (morning and evening) during the four-week treatment period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 4
Secondary outcomes (14)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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..
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 4 weeks
Rescue Medication Use
To determine the change from baseline in paracetamol rescue medication use during oral LAT8881 administration, compared with placebo.
Measured: 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
Measured: 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
Measured: 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
Measured: Day 1 and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start9 Apr 2019
- Primary completion19 Apr 2020
- Study completion3 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuropathic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lateral Pharma Pty Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03865953
- Sponsor's protocol ID
- LAT-NP-001
- Other IDs
- 2018-004534-15, 2018
- Status last verified
- Apr 2021
- First submitted
- 2 Mar 2019
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: This is an Early Proof of Concept study