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| Name | Class |
|---|---|
| Southern Star Research | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LAT8881 | Experimental | In Part A, LAT8881 will be given as a single intravenous infusion on separate days at doses of 0.8, 1.2 and 1.8 mg/kg. In Part B, LAT8881 will be given as a single intravenous infusion. The dose will be determined from the results of Part A. |
|
| Placebo | Placebo Comparator | Matching placebo will be given as a single intravenous infusion in Part A and Part B |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LAT8881 | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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)
| From first dose of LAT8881 to end of study visit (Day 14) |
| 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 | From start of infusion to 6 hours after start of infusion |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Up to 6 hours after the start of each infusion |
| Time to Maximum Plasma LAT8881 Concentration (Tmax) After Intravenous LAT8881 (Part A) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Key Inclusion Criteria:
For PART A, the following inclusion criteria apply:
For PART B, the following key inclusion criteria apply:
Key Exclusion Criteria:
The following key exclusion criteria apply for both PART A and PART B:
The following additional key exclusion criteria apply to PART B:
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| Name | Affiliation | Role |
|---|---|---|
| Guy Ludbrook, MBBS | Royal Adelaide Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PARC Clinical Research | Adelaide | South Australia | 5000 | Australia |
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Following a pre-planned interim analysis, Part B of the study was closed to enrolment after 17 subjects had completed the study.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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 |
| FG005 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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)
| Safety population. This population included all subjects who received at least one dose of IMP and had at least one post dose safety assessment. | Posted | Number | participants | From first dose of LAT8881 to end of study visit (Day 14) |
|
All events occurring during and following the first administration of IMP were reported as adverse events until the completion of the End of Study Evaluation visit (Day 14 for Part A, Day 9 for Part B).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A, LAT8881 0.8 mg/kg | LAT8881 was given as a single intravenous infusion at a dose of 0.8 mg/kg |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Stuart Mudge | Lateral Pharma | +61424588904 | sm@lateral-pharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 3, 2023 | May 7, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 15, 2023 | Aug 31, 2024 | SAP_001.pdf |
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The crossover study (Part B) is preceded by a single ascending dose study (Part A)
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| Placebo | Drug | Matching placebo'given as a single intravenous infusion at all dose levels |
|
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 |
| Up to 6 hours after the start of each infusion |
| 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. | Up to 6 hours after the start of each infusion |
| 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. | Up to 6 hours after the start of each infusion |
| 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. | 6 hours after the start of each infusion |
| 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
| From start of infusion to end of study visit (Day 9) |
| From start of infusion to 6 hours after start of infusion |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | 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 |
| BG005 | 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 |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Part A, LAT8881 1.2 mg/kg |
LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg |
| OG002 | Part A, LAT8881 1.8 mg/kg | LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg |
| OG003 | Part A, Placebo | Placebo was given as a single intravenous infusion |
|
|
| 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 | Full Analysis Set. This population included all enrolled and randomised participants. | Posted | Mean | Standard Deviation | score on a scale | From start of infusion to 6 hours after start of infusion |
|
|
|
|
| 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 | Subgroup of the pharmacokinetic population. Data for subjects with no measurable levels of LAT8881 were excluded from the summary. | Posted | Mean | Standard Deviation | ng/mL | Up to 6 hours after the start of each infusion |
|
|
|
| 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 | Subgroup of the pharmacokinetic population. Data for a subject with no measurable levels of LAT8881 were excluded from the summary. | Posted | Mean | Standard Deviation | hours | Up to 6 hours after the start of each infusion |
|
|
|
| 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. | 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 | Posted | Mean | Standard Deviation | ng/mL*h | Up to 6 hours after the start of each infusion |
|
|
|
| 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. | 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 | Posted | Mean | Standard Deviation | hours | Up to 6 hours after the start of each infusion |
|
|
|
| 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. | PGIC was measured in the Full Analysis Set. This population consisted of all subjects who were enrolled and randomised into the study | Posted | Count of Participants | Participants | 6 hours after the start of each infusion |
|
|
|
| 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
| 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. | Posted | Number | participants | From start of infusion to end of study visit (Day 9) |
|
|
|
| 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. | Full analysis set. This population included all subjects who were enrolled and randomised into the study. | Posted | Mean | Standard Deviation | score on a scale | From start of infusion to 6 hours after start of infusion |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 1 |
| 6 |
| EG001 | Part A, LAT8881 1.2 mg/kg | LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg | 0 | 6 | 0 | 6 | 1 | 6 |
| EG002 | Part A, LAT8881 1.8 mg/kg | LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg | 0 | 6 | 0 | 6 | 2 | 6 |
| EG003 | Part A, Placebo | Placebo was given as a single intravenous infusion | 0 | 6 | 0 | 6 | 2 | 6 |
| EG004 | Part B, LAT8881 | LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg | 0 | 17 | 0 | 17 | 5 | 17 |
| EG005 | Part B, Placebo | Placebo was given as a single intravenous infusion | 0 | 17 | 0 | 17 | 4 | 17 |
| Dizziness | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 24.1 | Systematic Assessment |
|
| Tachyardia | Cardiac disorders | MedDRA 24.1 | Systematic Assessment |
|
| Dysphoria | Psychiatric disorders | MedDRA 24.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 24.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 24.1 | Systematic Assessment |
|
| Reflex gastritus | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Hyperhydrosis | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 24.1 | Systematic Assessment |
|
Every participating investigator agrees to keep all information and results concerning the study and the investigational product confidential for as long as the data remain unpublished.
| Change from pre-dose score at 0.25 hours |
|
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| Change from pre-dose score at 0.5 hours |
|
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| Change from pre-dose score at 0.75 hours |
|
|
| Change from pre-dose score at 1.0 hours |
|
|
| Change from pre-dose score at 1.5 hours |
|
|
| Change from pre-dose score at 2 hours |
|
|
| Change from pre-dose score at 2.5 hours |
|
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| Change from pre-dose score at 3 hours |
|
|
| Change from pre-dose score at 3.5 hours |
|
|
| Change from pre-dose score at 4 hours |
|
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| Change from pre-dose score at 5 hours |
|
|
| Change from pre-dose score at 6 hours |
|
|
| Change in VAS score from baseline at 0.5 hours | Mixed Models Analysis | 0.3983 | No adjustment for multiple comparisons has been made due to the exploratory nature of the study | Mean Difference (Net) | -0.32 | 2-Sided | 95 | -1.09 | 0.44 | Difference is LAT8881 minus placebo | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 0.75 hours | Mixed Models Analysis | 0.4890 | No adjustment for multiple comparisons was made due to the exploratory nature of the study | Mean Difference (Net) | -0.26 | 2-Sided | 95 | -1.03 | 0.5 | Difference is LAT8881 minus placebo | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 1 hour | Mixed Models Analysis | 0.5903 | No adjustment for multiple comparisons was made due to the exploratory nature of the study | Mean Difference (Net) | -0.21 | 2-Sided | 95 | -0.97 | 0.56 | Difference is LAT8881 minus placebo | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 1.5 hours | Mixed Models Analysis | 0.7352 | No adjustment for multiple comparisons was made due to the exploratory nature of the study. | Mean Difference (Net) | -0.13 | 2-Sided | 95 | -0.90 | 0.64 | Difference is LAT8881 minus placebo. | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 2 hours | Mixed Models Analysis | 0.6892 | No adjustment for multiple comparisons was made due to the exploratory nature of the study. | Mean Difference (Net) | -0.15 | 2-Sided | 95 | -0.92 | 0.61 | Difference is LAT8881 minus placebo. | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 2.5 hours | Mixed Models Analysis | 0.9767 | No adjustment for multiple comparisons was made due to the exploratory nature of the study. | Mean Difference (Net) | -0.01 | 2-Sided | 95 | -0.78 | 0.76 | Difference is LAT8881 minus placebo. | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 3 hours | Mixed Models Analysis | 0.3964 | No adjustment for multiple comparisons was made due to the exploratory nature of the study. | Median Difference (Net) | 0.32 | 2-Sided | 95 | -0.44 | 1.09 | Difference is LAT8881 minus placebo. | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 3.5 hours | Mixed Models Analysis | 0.5669 | No adjustment for multiple comparisons was made due to the exploratory nature of the study. | Mean Difference (Net) | 0.22 | 2-Sided | 95 | -0.55 | 0.98 | Difference is LAT8881 minus placebo. | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 4 hours | Mixed Models Analysis | 0.7006 | No adjustment for multiple comparisons was made due to the exploratory nature of the study. | Mean Difference (Net) | -0.15 | 2-Sided | 95 | -0.91 | 0.62 | Difference is LAT8881 minus placebo. | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 5 hours | Mixed Models Analysis | 0.7940 | No adjustment for multiple comparisons was made due to the exploratory nature of the study. | Mean Difference (Net) | -0.10 | 2-Sided | 95 | -0.87 | 0.67 | Difference is LAT8881 minus placebo. | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. |
| Change from baseline VAS score at 6 hours | Mixed Models Analysis | No adjustment for multiple comparisons was made due to the exploratory nature of the study. | 0.6892 | Mean Difference (Net) | -0.15 | 2-Sided | 95 | -0.92 | 0.61 | Superiority | No formal sample size estimation was undertaken due to the exploratory nature of the study. Analysis was based a mixed model repeated measures model, with fixed-effects including treatment, time point and period factors. Baseline was included as a covariate. Random effects for participants and participant by period were also included. | Difference is LAT8881 minus placebo. |
| Slightly improved |
|
| No change |
|
| Slightly worse |
|
| Much worse |
|
| Very much worse |
|
| Adverse event leading to discontinuation |
|
| Adverse event of Grade 3 or 4 severity |
|
| VAS change from baseline at 0.5 hours |
|
| VAS change from baseline at 0.75 hours |
|
| VAS change from baseline at 1 hour |
|
| VAS change from baseline at 1.5 hours |
|
| VAS change from baseline at 2 hours |
|
| VAS change from baseline at 2.5 hours |
|
| VAS change from baseline at 3 hours |
|
| VAS change from baseline at 3.5 hours |
|
| VAS change from baseline at 4 hours |
|
| VAS change from baseline at 5 hours |
|
| VAS change from baseline at 6 hours |
|