Clinical trial NCT03865953: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuropathic Pain
Diabetic Peripheral Neuropathy (DPN)
Post Herpetic Neuralgia (PHN)
Lead sponsor: Lateral Pharma Pty Ltd
Sponsor class: INDUSTRY
First posted: 2019-03-07
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Absolute Change in Mean Pain Score, Using an 11 Point Numeric Pain Rating Scale (NPRS)
timeFrame: Baseline to Week 4
Secondary outcomes:
measure: Change in NPRS Score After the First and Last Dose of LAT8881 and Placebo
timeFrame: Pre-dose, 0.5,1,2,4 and 6 hours after the first and last dose of LAT8881 and placebo
measure: Change in Mean Pain Scores After 1, 2 and 3 Weeks of Treatment, Using NPRS
timeFrame: 1,2 and 3 weeks
measure: 30% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale.
timeFrame: 4 weeks
measure: 50% Responder Rate in Oral LAT8881 Compared With Placebo, as Assessed by the Numeric Pain Rating Scale.
timeFrame: 4 weeks
measure: Maximum Change in Mean NPRS
timeFrame: 1,2,3 or 4 weeks
measure: Change in Functioning as Assessed by the Brief Pain Inventory Interference Scale (BPI)
timeFrame: 4 weeks
measure: Change in Pain Characteristics and Intensity, as Assessed by the Short Form McGill Pain Questionnaire (SF-MPQ-2)
timeFrame: 4 weeks
measure: Change in Neuropathic Pain Symptoms, as Assessed by Neuropathic Pain Symptom Inventory (NPSI)
timeFrame: 4 weeks
measure: Change in Emotional Functioning, as Assessed by the Beck Depression Inventory-II
timeFrame: 4 weeks
measure: Patient Global Impression of Change Score
timeFrame: 4 weeks
measure: Rescue Medication Use
timeFrame: Weekly over four-week treatment
measure: Maximum Plasma Concentration of LAT8881 (Cmax) After Oral LAT8881
timeFrame: Day 1 and Day 28
measure: Time to Maximum Plasma Concentration of LAT8881 (Tmax)
timeFrame: Day 1 and day 28
measure: Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf)
timeFrame: Day 1 and Day 28
Other outcomes:
Locations:
city: Kanwal
country: Australia
facility: Paratus Clinical Research Kanwal
state: New South Wales
city: Sydney
country: Australia
facility: Paratus Clinical Research Blacktown
state: New South Wales
city: Brisbane
country: Australia
facility: AusTrials
state: Queensland
city: Melbourne
country: Australia
facility: Emeritus Research Services
state: Victoria
city: Bristol
country: United Kingdom
facility: University of Bristol
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
Study officials:
References: