Radiculopathy Lumbar
Conditions
Brief summary
The study consists of two parts. Part A will evaluate the safety and tolerability of intravenous LAT8881 in healthy volunteers using an ascending dose schedule. Part B will evaluate the analgesic efficacy of a single intravenous dose of LAT8881, compared with placebo, in patients with lumbar radicular pain. Healthy volunteers are not accepted for Part B.
Detailed description
Part A of this study is a double-blind, randomized, placebo-controlled, single ascending dose study of intravenous administration of LAT8881 over 5 minutes in healthy volunteers. Each participant has three treatment days, 1 infusion per dosing day, on Days 1, 4 and 7 as well as two short visits for safety blood sampling on Days 3 and 6. Subjects in Part A are randomized to receive placebo and LAT8881 according to the following treatment sequences. Two subjects are allocated to each treatment sequence, a total of eight subjects overall. 0.8 mg/kg/1.2 mg/kg/1.8 mg/kg; 0.8 mg/kg/1.2 mg/kg/Placebo; 0.8 mg/kg/Placebo/1.8 mg/kg; Placebo/1.2 mg/kg/1.8 mg/kg. Part B of this study is is a placebo-controlled randomized double blind cross-over safety and efficacy study of LAT8881 in up to 20 patients with lumbar radicular pain. Participants will be randomly assigned to one of two groups, to receive either LAT8881 then placebo or placebo then LAT8881. Participants will receive either a single dose of LAT8881 \[the Maximum Tolerated Dose from Part A of the study\] or placebo via intravenous administration over 5 minutes on two consecutive days.
Interventions
DRUGLAT8881
In Part A, LAT8881 will be given as a single intravenous infusion at doses of 0.8, 1.2 and 1.8 mg/kg. In Part B, a single intravenous infusion of LAT8881 will be given, the dose to be determined by the results in Part A
DRUGPlacebo
Matching placebo'given as a single intravenous infusion at all dose levels
Sponsors
Southern Star Research
Lateral Pharma Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
The crossover study (Part B) is preceded by a single ascending dose study (Part A)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: For PART A, the following inclusion criteria apply: * Male or female healthy participants, aged 18-49 years inclusive at screening; * Body mass index of ≥ 19.0 kg/m2 to ≤ 32.0 kg/m2 at screening; * Female participants must not be pregnant or breastfeeding * Male participants with a female partner of childbearing potential must use highly effective contraception for 60 days after the last dose of study treatment For PART B, the following key inclusion criteria apply: * Male or female participants with unilateral pain, aged 18 years and above at screening; * Body mass index of ≥ 19.0 kg/m2 at screening. * Female participants must not be pregnant or breastfeeding * Male participants with a female partner of childbearing potential must use highly effective contraception for 60 days after the last dose of study treatment * Presenting with a history of unilateral pain, radiating into a lower limb, of lancinating, burning, stabbing or electric quality, of duration of \>3 months. * Pain scores (NRS) for average daily leg pain at rest at the relevant nerve root of a mean of ≥4/10 and ≤9/10 for 3 days prior to treatment, with a minimum of \>3/10 on any day. * Demonstration of disc herniation within 6 months by CT or MRI at a segmental level consistent with the clinical features. * The site of disc herniation must affect L1-2, L2-3, L3-4, L4-5 or L5-S1. * The patient is willing to keep all analgesic medication and other therapy usage stable or decreased in the week prior to, and a week after, IP administration. * The patient is in good general health, with the exception of the presenting condition under study Key
Exclusion criteria
The following key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | From start of infusion to 6 hours after start of infusion | Change in pain from baseline is measured on on a 0-10 Visual Analogue Scale (VAS). The VAS consists of a 10 cm line with two endpoints representing 0 (no pain) and 10 (pain as bad as it could possibly be). The subject is asked to rate their current level of pain by placing a mark on the line and the distance from 0 is measured to provide a pain intensity score out of 10. VAS measurements are taken as the infusion starts and at 15 minute intervals for the first hour, then every thirty minutes for an additional two hours, then hourly until 6 hours from infusion commencement |
| The Number of Participants With Adverse Events by Dose (Part A) | From first dose of LAT8881 to end of study visit (Day 14) | The number of participants in Part A with the following adverse events will be reported by dose (with all placebo subjects combined) * All adverse events * Serious adverse events * Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) * Adverse events by intensity * Adverse events by relationship to IMP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Plasma LAT8881 Concentration (Tmax) After Intravenous LAT8881 (Part A) | Up to 6 hours after the start of each infusion | LAT8881 was measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration |
| Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) After Intravenous LAT8881 (Part A) | Up to 6 hours after the start of each infusion | LAT8881 was measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. (AUC0-inf) was calculated only if there were at least three quantifiable data points. |
| Patient General Impression of Change (Part B) | 6 hours after the start of each infusion | The Patient General Impression of Change (PGIC) is a single-item rating by subjects of their improvement with treatment during a clinical trial. Participants were asked to select one of the following options after each treatment: very much improved, much improved, slightly improved, no change, slightly worse, much worse, very much worse. |
| The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | From start of infusion to end of study visit (Day 9) | The number of participants in Part B with the following adverse events will be reported after placebo and after intravenous LAT8881 * All adverse events * Serious adverse events * Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) * Adverse events by intensity * Adverse events by relationship to IMP |
| Terminal Elimination Half Life (T1/2), (Part A) | Up to 6 hours after the start of each infusion | LAT8881 was measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. The terminal elimination half life was only determined if there were at least three quantifiable elimination phase data points. |
| Maximum Plasma LAT8881 Concentration (Cmax) After Intravenous LAT8881 (Part A) | Up to 6 hours after the start of each infusion | LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | From start of infusion to 6 hours after start of infusion | Change in pain from baseline is measured on a 0-10 Visual Analogue Scale (VAS). The VAS consists of a 10 cm line with two endpoints representing 0 (no pain) and 10 (pain as bad as it could possibly be). The subject is asked to rate their current level of pain on leg raising by placing a mark on the line and the distance from 0 is measured to provide a pain intensity score out of 10. VAS measurements are taken as the infusion starts and at 15 minute intervals for the first hour, then every thirty minutes for an additional two hours, then hourly until 6 hours from infusion commencement. Each measurement ranges from 0 to 10. The difference from the pre-dose score is calculated at specified timepoints up to 6 hours post-dose. |
Countries
Australia
Participant flow
Recruitment details
The study was conducted in two parts. Part A was a single ascending dose study of intravenous LAT8881 in healthy volunteers. The second part of the study (Part B) was initiated after completion of Part A and was a crossover study of LAT8881 in subjects with lumbar radicular pain. Both parts of the study were randomized, placebo-controlled and double-blinded.
Pre-assignment details
Following a pre-planned interim analysis, Part B of the study was closed to enrolment after 17 subjects had completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Part A (0.8 mg/kg; 1.2 mg/kg; 1.8 mg/kg) Doses were administered as a single intravenous infusion on Days 1, 4 and 7 | 2 |
| Part A (0.8 mg/kg; 1.2 mg/kg; Placebo) Doses were administered as a single intravenous infusion on Days 1, 4 and 7 | 2 |
| Part A (0.8 mg/kg; Placebo; 1.8 mg/kg) Doses were administered as a single intravenous infusion on Days 1, 4 and 7 | 2 |
| Part A (Placebo; 1.2 mg/kg; 1.8 mg/kg) Doses were administered as a single intravenous infusion on Days 1, 4 and 7 | 3 |
| Part B, LAT8881/Placebo LAT8881 was given as a single intravenous infusion on Day 1 at a dose of 1.8 mg/kg. Placebo was administered as a single intravenous infusion on the following day | 8 |
| Part B Placebo/LAT8881 Placebo was administered as a single intravenous infusion on Day 1. LAT8881 was given as a single intravenous infusion on the following day at a dose of 1.8 mg/kg | 9 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A (0.8 mg/kg; 1.2 mg/kg; 1.8 mg/kg) | Part A (0.8 mg/kg; 1.2 mg/kg; Placebo) | Part A (0.8 mg/kg; Placebo; 1.8 mg/kg) | Part A (Placebo; 1.2 mg/kg; 1.8 mg/kg) | Part B, LAT8881/Placebo | Part B Placebo/LAT8881 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 26.0 years STANDARD_DEVIATION 4.2 | 28.5 years STANDARD_DEVIATION 3.5 | 21.0 years STANDARD_DEVIATION 1.4 | 26.0 years STANDARD_DEVIATION 4 | 51.9 years STANDARD_DEVIATION 13.5 | 56.0 years STANDARD_DEVIATION 11.9 | 44.2 years STANDARD_DEVIATION 17.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 7 Participants | 9 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Australia | 2 participants | 2 participants | 2 participants | 3 participants | 8 participants | 9 participants | 26 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants | 3 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 1 / 6 | 1 / 6 | 2 / 6 | 2 / 6 | 5 / 17 | 4 / 17 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 17 | 0 / 17 |
Outcome results
Primary
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B)
Change in pain from baseline is measured on on a 0-10 Visual Analogue Scale (VAS). The VAS consists of a 10 cm line with two endpoints representing 0 (no pain) and 10 (pain as bad as it could possibly be). The subject is asked to rate their current level of pain by placing a mark on the line and the distance from 0 is measured to provide a pain intensity score out of 10. VAS measurements are taken as the infusion starts and at 15 minute intervals for the first hour, then every thirty minutes for an additional two hours, then hourly until 6 hours from infusion commencement
Time frame: From start of infusion to 6 hours after start of infusion
Population: Full Analysis Set. This population included all enrolled and randomised participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 0.5 hours | -0.8 score on a scale | Standard Deviation 2 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 2.5 hours | -0.8 score on a scale | Standard Deviation 2.1 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 1.0 hours | -1.1 score on a scale | Standard Deviation 2.2 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 3 hours | -0.6 score on a scale | Standard Deviation 1.9 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 0.25 hours | -0.8 score on a scale | Standard Deviation 1.8 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 3.5 hours | -0.8 score on a scale | Standard Deviation 2.1 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 1.5 hours | -0.8 score on a scale | Standard Deviation 1.8 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 4 hours | -0.9 score on a scale | Standard Deviation 2 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 0.75 hours | -1.0 score on a scale | Standard Deviation 1.8 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 5 hours | -1.0 score on a scale | Standard Deviation 2.2 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 2 hours | -0.8 score on a scale | Standard Deviation 2 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 6 hours | -1.2 score on a scale | Standard Deviation 2 |
| Part A, LAT8881 0.8 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Pre-dose VAS score | 3.7 score on a scale | Standard Deviation 2.7 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 6 hours | -0.8 score on a scale | Standard Deviation 1.4 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Pre-dose VAS score | 3.1 score on a scale | Standard Deviation 2.3 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 0.25 hours | -0.3 score on a scale | Standard Deviation 1.1 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 0.5 hours | -0.3 score on a scale | Standard Deviation 1.5 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 0.75 hours | -0.5 score on a scale | Standard Deviation 1.5 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 1.0 hours | -0.6 score on a scale | Standard Deviation 1.4 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 1.5 hours | -0.5 score on a scale | Standard Deviation 1.1 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 2 hours | -0.4 score on a scale | Standard Deviation 1.4 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 2.5 hours | -0.6 score on a scale | Standard Deviation 1.4 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 3 hours | -0.7 score on a scale | Standard Deviation 1.5 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 3.5 hours | -0.8 score on a scale | Standard Deviation 1.4 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 4 hours | -0.5 score on a scale | Standard Deviation 1.5 |
| Part A, LAT8881 1.2 mg/kg | Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Change from pre-dose score at 5 hours | -0.7 score on a scale | Standard Deviation 1.6 |
Comparison: Change from baseline VAS score at 0.25 hoursp-value: 0.519695% CI: [-1.02, 0.52]Mixed Models Analysis
Comparison: Change in VAS score from baseline at 0.5 hoursp-value: 0.398395% CI: [-1.09, 0.44]Mixed Models Analysis
Comparison: Change from baseline VAS score at 0.75 hoursp-value: 0.48995% CI: [-1.03, 0.5]Mixed Models Analysis
Comparison: Change from baseline VAS score at 1 hourp-value: 0.590395% CI: [-0.97, 0.56]Mixed Models Analysis
Comparison: Change from baseline VAS score at 1.5 hoursp-value: 0.735295% CI: [-0.9, 0.64]Mixed Models Analysis
Comparison: Change from baseline VAS score at 2 hoursp-value: 0.689295% CI: [-0.92, 0.61]Mixed Models Analysis
Comparison: Change from baseline VAS score at 2.5 hoursp-value: 0.976795% CI: [-0.78, 0.76]Mixed Models Analysis
Comparison: Change from baseline VAS score at 3 hoursp-value: 0.396495% CI: [-0.44, 1.09]Mixed Models Analysis
Comparison: Change from baseline VAS score at 3.5 hoursp-value: 0.566995% CI: [-0.55, 0.98]Mixed Models Analysis
Comparison: Change from baseline VAS score at 4 hoursp-value: 0.700695% CI: [-0.91, 0.62]Mixed Models Analysis
Comparison: Change from baseline VAS score at 5 hoursp-value: 0.79495% CI: [-0.87, 0.67]Mixed Models Analysis
Comparison: Change from baseline VAS score at 6 hoursp-value: 0.689295% CI: [-0.92, 0.61]Mixed Models Analysis
Primary
The Number of Participants With Adverse Events by Dose (Part A)
The number of participants in Part A with the following adverse events will be reported by dose (with all placebo subjects combined) * All adverse events * Serious adverse events * Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) * Adverse events by intensity * Adverse events by relationship to IMP
Time frame: From first dose of LAT8881 to end of study visit (Day 14)
Population: Safety population. This population included all subjects who received at least one dose of IMP and had at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A, LAT8881 0.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Adverse event of Grade 3 or 4 severity | 0 participants |
| Part A, LAT8881 0.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Serious adverse event | 0 participants |
| Part A, LAT8881 0.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Adverse events related to IMP (possibly, probably or definitely) | 0 participants |
| Part A, LAT8881 0.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) | 0 participants |
| Part A, LAT8881 0.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Any adverse event | 1 participants |
| Part A, LAT8881 1.2 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) | 0 participants |
| Part A, LAT8881 1.2 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Adverse event of Grade 3 or 4 severity | 0 participants |
| Part A, LAT8881 1.2 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Adverse events related to IMP (possibly, probably or definitely) | 0 participants |
| Part A, LAT8881 1.2 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Serious adverse event | 0 participants |
| Part A, LAT8881 1.2 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Any adverse event | 1 participants |
| Part A, LAT8881 1.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) | 0 participants |
| Part A, LAT8881 1.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Any adverse event | 2 participants |
| Part A, LAT8881 1.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Serious adverse event | 0 participants |
| Part A, LAT8881 1.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Adverse event of Grade 3 or 4 severity | 0 participants |
| Part A, LAT8881 1.8 mg/kg | The Number of Participants With Adverse Events by Dose (Part A) | Adverse events related to IMP (possibly, probably or definitely) | 2 participants |
| Part A, Placebo | The Number of Participants With Adverse Events by Dose (Part A) | Adverse event of Grade 3 or 4 severity | 0 participants |
| Part A, Placebo | The Number of Participants With Adverse Events by Dose (Part A) | Serious adverse event | 0 participants |
| Part A, Placebo | The Number of Participants With Adverse Events by Dose (Part A) | Any adverse event | 2 participants |
| Part A, Placebo | The Number of Participants With Adverse Events by Dose (Part A) | Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) | 0 participants |
| Part A, Placebo | The Number of Participants With Adverse Events by Dose (Part A) | Adverse events related to IMP (possibly, probably or definitely) | 1 participants |
Secondary
Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) After Intravenous LAT8881 (Part A)
LAT8881 was measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. (AUC0-inf) was calculated only if there were at least three quantifiable data points.
Time frame: Up to 6 hours after the start of each infusion
Population: Subgroup of the pharmacokinetic population. Data for subjects with no measurable levels of LAT8881 were excluded from the summary. (AUC0-inf) was not calculated as the criteria of at least three quantifiable data points was not met
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A, LAT8881 0.8 mg/kg | Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) After Intravenous LAT8881 (Part A) | NA ng/mL*h |
| Part A, LAT8881 1.2 mg/kg | Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) After Intravenous LAT8881 (Part A) | NA ng/mL*h |
| Part A, LAT8881 1.8 mg/kg | Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) After Intravenous LAT8881 (Part A) | NA ng/mL*h |
Secondary
Maximum Plasma LAT8881 Concentration (Cmax) After Intravenous LAT8881 (Part A)
LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration
Time frame: Up to 6 hours after the start of each infusion
Population: Subgroup of the pharmacokinetic population. Data for subjects with no measurable levels of LAT8881 were excluded from the summary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A, LAT8881 0.8 mg/kg | Maximum Plasma LAT8881 Concentration (Cmax) After Intravenous LAT8881 (Part A) | 12.6 ng/mL | Standard Deviation 19.1 |
| Part A, LAT8881 1.2 mg/kg | Maximum Plasma LAT8881 Concentration (Cmax) After Intravenous LAT8881 (Part A) | 10.2 ng/mL | Standard Deviation 12.9 |
| Part A, LAT8881 1.8 mg/kg | Maximum Plasma LAT8881 Concentration (Cmax) After Intravenous LAT8881 (Part A) | 13.8 ng/mL | Standard Deviation 14.1 |
Secondary
Patient General Impression of Change (Part B)
The Patient General Impression of Change (PGIC) is a single-item rating by subjects of their improvement with treatment during a clinical trial. Participants were asked to select one of the following options after each treatment: very much improved, much improved, slightly improved, no change, slightly worse, much worse, very much worse.
Time frame: 6 hours after the start of each infusion
Population: PGIC was measured in the Full Analysis Set. This population consisted of all subjects who were enrolled and randomised into the study
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A, LAT8881 0.8 mg/kg | Patient General Impression of Change (Part B) | Slightly improved | 4 Participants |
| Part A, LAT8881 0.8 mg/kg | Patient General Impression of Change (Part B) | Slightly worse | 1 Participants |
| Part A, LAT8881 0.8 mg/kg | Patient General Impression of Change (Part B) | Much improved | 3 Participants |
| Part A, LAT8881 0.8 mg/kg | Patient General Impression of Change (Part B) | Much worse | 0 Participants |
| Part A, LAT8881 0.8 mg/kg | Patient General Impression of Change (Part B) | Very much worse | 0 Participants |
| Part A, LAT8881 0.8 mg/kg | Patient General Impression of Change (Part B) | No change | 7 Participants |
| Part A, LAT8881 0.8 mg/kg | Patient General Impression of Change (Part B) | Very much improved | 2 Participants |
| Part A, LAT8881 1.2 mg/kg | Patient General Impression of Change (Part B) | Much worse | 0 Participants |
| Part A, LAT8881 1.2 mg/kg | Patient General Impression of Change (Part B) | Very much improved | 0 Participants |
| Part A, LAT8881 1.2 mg/kg | Patient General Impression of Change (Part B) | Much improved | 2 Participants |
| Part A, LAT8881 1.2 mg/kg | Patient General Impression of Change (Part B) | Slightly improved | 11 Participants |
| Part A, LAT8881 1.2 mg/kg | Patient General Impression of Change (Part B) | No change | 4 Participants |
| Part A, LAT8881 1.2 mg/kg | Patient General Impression of Change (Part B) | Slightly worse | 0 Participants |
| Part A, LAT8881 1.2 mg/kg | Patient General Impression of Change (Part B) | Very much worse | 0 Participants |
Secondary
Terminal Elimination Half Life (T1/2), (Part A)
LAT8881 was measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. The terminal elimination half life was only determined if there were at least three quantifiable elimination phase data points.
Time frame: Up to 6 hours after the start of each infusion
Population: Subgroup of the pharmacokinetic population. Data for a subject with no measurable levels of LAT8881 were excluded from the summary. Terminal half-life could not be determined as the criteria of at least three quantifiable elimination phase data points was not met
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A, LAT8881 0.8 mg/kg | Terminal Elimination Half Life (T1/2), (Part A) | NA hours |
| Part A, LAT8881 1.2 mg/kg | Terminal Elimination Half Life (T1/2), (Part A) | NA hours |
| Part A, LAT8881 1.8 mg/kg | Terminal Elimination Half Life (T1/2), (Part A) | NA hours |
Secondary
The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B)
The number of participants in Part B with the following adverse events will be reported after placebo and after intravenous LAT8881 * All adverse events * Serious adverse events * Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) * Adverse events by intensity * Adverse events by relationship to IMP
Time frame: From start of infusion to end of study visit (Day 9)
Population: The safety population consisted of all randomized participants who received at least one dose of IMP and had at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A, LAT8881 0.8 mg/kg | The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Any adverse event | 5 participants |
| Part A, LAT8881 0.8 mg/kg | The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Serious adverse event | 0 participants |
| Part A, LAT8881 0.8 mg/kg | The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Adverse event leading to discontinuation | 0 participants |
| Part A, LAT8881 0.8 mg/kg | The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Adverse event of Grade 3 or 4 severity | 0 participants |
| Part A, LAT8881 1.2 mg/kg | The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Adverse event of Grade 3 or 4 severity | 0 participants |
| Part A, LAT8881 1.2 mg/kg | The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Any adverse event | 4 participants |
| Part A, LAT8881 1.2 mg/kg | The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Adverse event leading to discontinuation | 0 participants |
| Part A, LAT8881 1.2 mg/kg | The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) | Serious adverse event | 0 participants |
Secondary
Time to Maximum Plasma LAT8881 Concentration (Tmax) After Intravenous LAT8881 (Part A)
LAT8881 was measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration
Time frame: Up to 6 hours after the start of each infusion
Population: Subgroup of the pharmacokinetic population. Data for a subject with no measurable levels of LAT8881 were excluded from the summary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A, LAT8881 0.8 mg/kg | Time to Maximum Plasma LAT8881 Concentration (Tmax) After Intravenous LAT8881 (Part A) | 0.08 hours | Standard Deviation 0 |
| Part A, LAT8881 1.2 mg/kg | Time to Maximum Plasma LAT8881 Concentration (Tmax) After Intravenous LAT8881 (Part A) | 0.08 hours | Standard Deviation 0 |
| Part A, LAT8881 1.8 mg/kg | Time to Maximum Plasma LAT8881 Concentration (Tmax) After Intravenous LAT8881 (Part A) | 0.08 hours | Standard Deviation 0 |
Other Pre-specified
The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch.
Change in pain from baseline is measured on a 0-10 Visual Analogue Scale (VAS). The VAS consists of a 10 cm line with two endpoints representing 0 (no pain) and 10 (pain as bad as it could possibly be). The subject is asked to rate their current level of pain on leg raising by placing a mark on the line and the distance from 0 is measured to provide a pain intensity score out of 10. VAS measurements are taken as the infusion starts and at 15 minute intervals for the first hour, then every thirty minutes for an additional two hours, then hourly until 6 hours from infusion commencement. Each measurement ranges from 0 to 10. The difference from the pre-dose score is calculated at specified timepoints up to 6 hours post-dose.
Time frame: From start of infusion to 6 hours after start of infusion
Population: Full analysis set. This population included all subjects who were enrolled and randomised into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 0.5 hours | -0.8 score on a scale | Standard Deviation 1.2 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 2.5 hours | -1.0 score on a scale | Standard Deviation 1.9 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 1 hour | -1.1 score on a scale | Standard Deviation 1.7 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 3 hours | -1.1 score on a scale | Standard Deviation 1.9 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 0.25 hours | -0.3 score on a scale | Standard Deviation 1.7 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 3.5 hours | -1.3 score on a scale | Standard Deviation 2.1 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 1.5 hours | -1.2 score on a scale | Standard Deviation 1.9 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 4 hours | -1.3 score on a scale | Standard Deviation 2.6 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 0.75 hours | -1.1 score on a scale | Standard Deviation 1.4 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 5 hours | -1.6 score on a scale | Standard Deviation 2.2 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 2 hours | -0.9 score on a scale | Standard Deviation 1.9 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 6 hours | -1.3 score on a scale | Standard Deviation 2.1 |
| Part A, LAT8881 0.8 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | Pre-dose VAS score | 5.2 score on a scale | Standard Deviation 2.6 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 6 hours | -1.2 score on a scale | Standard Deviation 2.2 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | Pre-dose VAS score | 4.8 score on a scale | Standard Deviation 2.4 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 0.25 hours | 0.2 score on a scale | Standard Deviation 0.9 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 0.5 hours | -0.3 score on a scale | Standard Deviation 1.3 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 0.75 hours | -0.2 score on a scale | Standard Deviation 1.5 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 1 hour | -0.2 score on a scale | Standard Deviation 1.5 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 1.5 hours | 0.0 score on a scale | Standard Deviation 1.5 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 2 hours | -0.3 score on a scale | Standard Deviation 1.5 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 2.5 hours | -0.1 score on a scale | Standard Deviation 1.6 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 3 hours | -0.4 score on a scale | Standard Deviation 1.7 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 3.5 hours | -0.4 score on a scale | Standard Deviation 1.7 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 4 hours | -0.6 score on a scale | Standard Deviation 2.2 |
| Part A, LAT8881 1.2 mg/kg | The Effect of LAT8881, Compared With Placebo, on VAS Pain Scores During a Straight-leg Nerve Stretch. | VAS change from baseline at 5 hours | -0.7 score on a scale | Standard Deviation 2 |