Complex Regional Pain Syndrome
Conditions
Keywords
Drug Therapy, Soticlestat, TAk-935
Brief summary
The purpose of this study is to investigate the effect of soticlestat (TAK-935) on calculated 24-hour average pain intensity by the numeric pain scale (NPS).
Detailed description
The drug being tested in this study is called soticlestat (TAK-935). Soticlestat is being tested to treat people with chronic complex regional pain syndrome (CRPS). This study will look at the efficacy, safety, and tolerability of soticlestat as an adjunctive therapy in participants with CRPS. The study will enroll approximately 24 patients. Participants will be randomly assigned (by chance, like flipping a coin) in 2:1 ratio to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): Soticlestat 100 mg tablets, 100, 200 or 300 mg twice daily (BID) Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient Participants will receive 100 mg soticlestat tablets or soticlestat matching placebo tablets, BID for Week 1, 2x100 mg soticlestat tablets or soticlestat matching placebo tablets, BID for Week 2 and followed by 3x100 mg soticlestat tablets or soticlestat matching placebo tablets, BID for Week 3. Dose will be uptitrated based on safety and tolerability in titration period. Participants will continue to receive the same dose in maintenance period. Dose adjustments during maintenance period may take place due to safety and tolerability. Participants will then enter Part B (optional) or taper period. In Part B all participants will receive soticlestat 2x100 mg tablets, BID for 1 Week, followed by soticlestat 3x100 mg tablets, BID for 1 Week. Dose will be uptitrated/downtitrated based on safety and tolerability in titration period (Part B), participants will continue to receive the same dose in maintenance period (Part B) and followed by a taper period. This multi-center trial will be conducted in United Kingdom. The overall time to participate in this study is approximately 36 weeks. Participants will make multiple visits to the clinic and will be contacted by telephone 15 days after last dose of study drug for a follow-up assessment.
Interventions
DRUGSoticlestat
Soticlestat tablets
DRUGPlacebo
Soticlestat matching placebo tablets
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participant meets the Budapest clinical diagnosis of complex regional pain syndrome (CRPS) at the screening visit and is at least 6 months since onset of symptoms. 2. Participant's pain medications and nondrug treatments must be stable (regimented per prescription) for 1 month prior to screening and remain stable throughout Part A. 3. Participant agrees to use a single previously prescribed rescue medication within the prescribed dose during Part A of the study and to record the daily use of these medications. 4. Participant must have an average 24-hour pain intensity score ≥4 and ≤9 on the 24-hour average pain intensity numeric pain scale (NPS) during screening/baseline. This score will be calculated by averaging the daily 24 hour pain intensity scores for the past seven days prior to randomization. The participant must have daily 24-hour pain intensity scores recorded for at least 6 of the past 7 days.
Exclusion criteria
1. Currently receiving intravenous (IV) or oral ketamine, history of IV or oral ketamine use within the past 6 weeks prior to screening, or planned use of IV or oral ketamine during this study. 2. Participant is receiving chronic opioid treatment at a dose that has not been stable 28 days prior to screening. 3. Participant is receiving chronic opioid treatment \>160 mg of morphine equivalent per day. 4. Participant has a positive drug screen for phencyclidine, amphetamine/ methamphetamine, or cocaine at screening. Cannabis is allowed.. 5. Participant is positive for hepatitis B or hepatitis C infection at screening. (Note that participants who have been vaccinated against hepatitis B \[hepatitis B surface antibody {Ab}-positive\] who are negative for other markers of prior hepatitis B infection \[eg, negative for hepatitis B core Ab\] are eligible. Also, note that participants who are positive for hepatitis C Ab are eligible if they have a negative hepatitis C viral load by quantitative polymerase chain reaction).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A | Baseline and Week 15 | The 24-hour average pain intensity was calculated from current pain intensity scores collected three times a day as measured by the electronic pain diary daily using NPS. NPS is an 11-point scale, where scores range from 0-10, 0= no pain to 10 = most pain imaginable. Negative change from Baseline indicated improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Considered Responders at the End of Part A | Week 15 | Response was defined as ≥ 30% improvement on the 24-hour pain intensity as assessed by the NPS score. The 24-hour average pain intensity was calculated from current pain intensity scores collected three times a day as measured by the electronic pain diary daily using NPS during Part A. NPS is an 11-point scale, where scores range from 0-10, 0= no pain to 10 = most pain imaginable. |
| Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Baseline and Week 15 | PROMIS-29 (v2.1) is a health-related quality of life survey assessing 7 domains with 4 questions on a 5-point Likert scale. Total raw domain scores are converted into T-scores from a reference population: Depression: 1=never to 5=always, T-scores:41.0-79.4; Physical function: 1=unable to do to 5=without any difficulty, T-scores: 22.5-57.0; Anxiety: 1=never to 5=always, T-scores: 40.3-81.6; Pain interference: 1=not at all to 5=very much, T-scores: 41.6-75.6; Fatigue: 1=not at all to 5=very much, T-scores: 33.7-75.8; Sleep disturbance: 1=very much to 5=not at all, T-scores: 32.0-73.3; Ability to participate in social roles or activities: 1=always to 5=never, T-scores: 27.5-64.2. High scores signify more of domain being measured. Thus, on symptom-oriented domains, higher scores=worse symptomatology and a negative change from Baseline indicates improvement. On function-oriented domains, higher score=better functioning and a positive change from Baseline indicates improvement. |
| Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Baseline and Week 15 | PROMIS-29 (v2.1) is a health-related quality of life survey assessing 7 domains with 4 questions on a 5-point Likert scale. Total raw domain scores are converted into T-scores from a reference population: Depression: 1=never to 5=always, T-scores:41.0-79.4; Physical function: 1=unable to do to 5=without any difficulty, T-scores: 22.5-57.0; Anxiety: 1=never to 5=always, T-scores: 40.3-81.6; Pain interference: 1=not at all to 5=very much, T-scores: 41.6-75.6; Fatigue: 1=not at all to 5=very much, T-scores: 33.7-75.8; Sleep disturbance: 1=very much to 5=not at all, T-scores: 32.0-73.3; Ability to participate in social roles or activities: 1=always to 5=never, T-scores: 27.5-64.2. High scores signify more of domain being measured. Thus, on symptom-oriented domains, higher scores=worse symptomatology and a negative change from Baseline indicates improvement. On function-oriented domains, higher score=better functioning and a positive change from Baseline indicates improvement. |
| Percent Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A | Baseline and Week 15 | The 24-hour average pain intensity was calculated from current pain intensity scores collected three times a day as measured by the electronic pain diary daily using NPS. NPS is an 11-point scale, where scores range from 0-10, 0= no pain to 10 = most pain imaginable. Negative percent change from Baseline indicated improvement. |
| Change From Baseline in Complex Regional Pain Syndrome (CSS) at the End of Part A | Baseline and Week 15 | Signs and symptoms reflecting the sensory, vasomotor, sudomotor/edema, and motor/trophic disturbances of CRPS had been incorporated into a clinically feasible CSS. Total CSS is a 16-point score which was calculated by the number of yes answers to the questions on the 8 symptoms and 8 signs when all 16 questions were answered. Negative change from Baseline indicates improvement. |
| Percent Change From Baseline in CSS at the End of Part A | Baseline and Week 15 | Signs and symptoms reflecting the sensory, vasomotor, sudomotor/edema, and motor/trophic disturbances of CRPS had been incorporated into a clinically feasible CSS. Total CSS is a 16-point score which was calculated by the number of yes answers to the questions on the 8 symptoms and 8 signs when all 16 questions were answered. Negative percent change from Baseline indicates improvement. |
| Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | Week 15 | The PGIC is a 7-point Likert scale to address the following question: Since beginning treatment at this clinic would you describe any changes (if any) in activity, limitations, symptoms, emotions and overall quality of life related to your painful condition compared to before treatment? Participants select from scale range of 1-7: very much improved (1); much improved (2); minimally improved (3); no change (4); minimally worse (5); much worse (6); very much worse (7). Only categories with at least 1 participant were reported. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at three investigative sites in United Kingdom (UK) from 23 July 2019 to 28 October 2020.
Pre-assignment details
Participants with a diagnosis of chronic complex regional pain syndrome (CRPS) were enrolled to receive soticlestat or placebo in Part A (Double-blind \[DB\] Treatment Period) and soticlestat in Part B (Open-label \[OL\] Treatment Period). Following completion of the Part A, participants had an option to continue into Part B.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Treatment Period - Part A: Placebo Soticlestat matching placebo tablets, orally, twice daily (BID) for Weeks 1, 2 and 3 in Double blind Titration Period. Soticlestat matching placebo tablets, orally BID for 12 weeks in Double blind Maintenance Period. Taper period (if participant did not continue to Part B): Dose of soticlestat matching placebo tablets was reduced to next lower dose every 3 days (maximum 6 days) until discontinuation. | 9 |
| Double-Blind Treatment Period - Part A: Soticlestat Soticlestat, tablet, orally, 100 mg BID for Week 1, followed by 2×100 mg tablets, soticlestat, orally BID for Week 2, further followed by 3×100 mg tablets, soticlestat, orally BID for Week 3. Dose was uptitrated every week based on safety and tolerability. Part A (Double blind Maintenance Period): 3×100 mg tablets, soticlestat, orally BID for 12 weeks. Dose was adjusted during Maintenance Period due to safety and tolerability. Taper Period (if participant did not continue to Part B): Dose of soticlestat was reduced to next lower dose every 3 days (maximum 6 days) until soticlestat was discontinued. | 15 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A: DB Treatment Period (15 Weeks) | Adverse Event | 0 | 1 | 0 |
| Part A: DB Treatment Period (15 Weeks) | Lost to Follow-up | 0 | 1 | 0 |
| Part A: DB Treatment Period (15 Weeks) | Reason not Specified | 1 | 1 | 0 |
| Part A: DB Treatment Period (15 Weeks) | Withdrawal by Subject | 2 | 0 | 0 |
| Part B: OL Extension Period (14 Weeks) | Adverse Event | 0 | 0 | 1 |
| Part B: OL Extension Period (14 Weeks) | Reason not Specified | 0 | 0 | 1 |
| Part B: OL Extension Period (14 Weeks) | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Double-Blind Treatment Period - Part A: Placebo | Double-Blind Treatment Period - Part A: Soticlestat | Total |
|---|---|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 13.51 | 42.1 years STANDARD_DEVIATION 10.27 | 41.0 years STANDARD_DEVIATION 11.4 |
| CRPS Severity Score (CSS) Total Score | 12.7 scores on a scale STANDARD_DEVIATION 1.73 | 12.9 scores on a scale STANDARD_DEVIATION 1.87 | 12.8 scores on a scale STANDARD_DEVIATION 1.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 14 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Numeric Pain Scale (NPS) Score | 6.33 scores on a scale | 6.33 scores on a scale | 6.33 scores on a scale |
| Patient-Reported Outcomes Measurement Information System (PROMIS-29) Version 2.1 Domain Score Ability to Participate in Social Roles and Activities | 40.03 t-score STANDARD_DEVIATION 6.205 | 39.11 t-score STANDARD_DEVIATION 4.723 | 39.45 t-score STANDARD_DEVIATION 5.213 |
| Patient-Reported Outcomes Measurement Information System (PROMIS-29) Version 2.1 Domain Score Anxiety | 46.30 t-score STANDARD_DEVIATION 11.906 | 51.94 t-score STANDARD_DEVIATION 8.873 | 49.83 t-score STANDARD_DEVIATION 10.248 |
| Patient-Reported Outcomes Measurement Information System (PROMIS-29) Version 2.1 Domain Score Depression | 47.31 t-score STANDARD_DEVIATION 12.523 | 47.27 t-score STANDARD_DEVIATION 8.868 | 47.28 t-score STANDARD_DEVIATION 10.12 |
| Patient-Reported Outcomes Measurement Information System (PROMIS-29) Version 2.1 Domain Score Fatigue | 57.17 t-score STANDARD_DEVIATION 8.427 | 60.55 t-score STANDARD_DEVIATION 8.28 | 59.28 t-score STANDARD_DEVIATION 8.321 |
| Patient-Reported Outcomes Measurement Information System (PROMIS-29) Version 2.1 Domain Score Pain Interference | 66.37 t-score STANDARD_DEVIATION 6.71 | 64.22 t-score STANDARD_DEVIATION 8.039 | 65.03 t-score STANDARD_DEVIATION 7.492 |
| Patient-Reported Outcomes Measurement Information System (PROMIS-29) Version 2.1 Domain Score Physical Function | 35.83 t-score STANDARD_DEVIATION 5.607 | 34.65 t-score STANDARD_DEVIATION 4.743 | 35.09 t-score STANDARD_DEVIATION 4.998 |
| Patient-Reported Outcomes Measurement Information System (PROMIS-29) Version 2.1 Domain Score Sleep Disturbance | 54.63 t-score STANDARD_DEVIATION 3.854 | 54.99 t-score STANDARD_DEVIATION 2.39 | 54.86 t-score STANDARD_DEVIATION 2.945 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 15 Participants | 24 Participants |
| Region of Enrollment United Kingdom | 9 Participants | 15 Participants | 24 Participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 15 | 0 / 18 |
| other Total, other adverse events | 9 / 9 | 12 / 15 | 10 / 18 |
| serious Total, serious adverse events | 0 / 9 | 3 / 15 | 0 / 18 |
Outcome results
Primary
Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A
The 24-hour average pain intensity was calculated from current pain intensity scores collected three times a day as measured by the electronic pain diary daily using NPS. NPS is an 11-point scale, where scores range from 0-10, 0= no pain to 10 = most pain imaginable. Negative change from Baseline indicated improvement.
Time frame: Baseline and Week 15
Population: Full Analysis Set for included all participants who were randomized, received at least 1 dose of study drug, and had at least one valid post-baseline value for the assessment of average 24-hour pain score. The data is reported for Part A in this outcome measure. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Treatment Period - Part A: Placebo | Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A | -0.74 scores on scale | Standard Deviation 1.614 |
| Double-Blind Treatment Period - Part A: Soticlestat | Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A | -1.05 scores on scale | Standard Deviation 1.31 |
Secondary
Change From Baseline in Complex Regional Pain Syndrome (CSS) at the End of Part A
Signs and symptoms reflecting the sensory, vasomotor, sudomotor/edema, and motor/trophic disturbances of CRPS had been incorporated into a clinically feasible CSS. Total CSS is a 16-point score which was calculated by the number of yes answers to the questions on the 8 symptoms and 8 signs when all 16 questions were answered. Negative change from Baseline indicates improvement.
Time frame: Baseline and Week 15
Population: Full Analysis Set for included all participants who were randomized, received at least 1 dose of study drug, and had at least one valid post-baseline value for the assessment of average 24-hour pain score. The data is reported for Part A in this outcome measure. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Treatment Period - Part A: Placebo | Change From Baseline in Complex Regional Pain Syndrome (CSS) at the End of Part A | -2.2 scores on scale | Standard Deviation 2.48 |
| Double-Blind Treatment Period - Part A: Soticlestat | Change From Baseline in Complex Regional Pain Syndrome (CSS) at the End of Part A | -3.1 scores on scale | Standard Deviation 3.12 |
p-value: 0.54t-test, 2 sided
Secondary
Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A
PROMIS-29 (v2.1) is a health-related quality of life survey assessing 7 domains with 4 questions on a 5-point Likert scale. Total raw domain scores are converted into T-scores from a reference population: Depression: 1=never to 5=always, T-scores:41.0-79.4; Physical function: 1=unable to do to 5=without any difficulty, T-scores: 22.5-57.0; Anxiety: 1=never to 5=always, T-scores: 40.3-81.6; Pain interference: 1=not at all to 5=very much, T-scores: 41.6-75.6; Fatigue: 1=not at all to 5=very much, T-scores: 33.7-75.8; Sleep disturbance: 1=very much to 5=not at all, T-scores: 32.0-73.3; Ability to participate in social roles or activities: 1=always to 5=never, T-scores: 27.5-64.2. High scores signify more of domain being measured. Thus, on symptom-oriented domains, higher scores=worse symptomatology and a negative change from Baseline indicates improvement. On function-oriented domains, higher score=better functioning and a positive change from Baseline indicates improvement.
Time frame: Baseline and Week 15
Population: Full Analysis Set for included all participants who were randomized, received at least 1 dose of study drug, and had at least one valid post-baseline value for the assessment of average 24-hour pain score. The data is reported for Part A in this outcome measure. Number analyzed are the number of participants with data available for analyses in the given category (domain).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Treatment Period - Part A: Placebo | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Depression | 1.15 t-score | Standard Deviation 10.011 |
| Double-Blind Treatment Period - Part A: Placebo | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Sleep Disturbance | 2.13 t-score | Standard Deviation 5.11 |
| Double-Blind Treatment Period - Part A: Placebo | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Anxiety | 3.29 t-score | Standard Deviation 10.348 |
| Double-Blind Treatment Period - Part A: Placebo | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Ability to Participate in Social Roles | 1.66 t-score | Standard Deviation 6.051 |
| Double-Blind Treatment Period - Part A: Placebo | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Fatigue | 0.45 t-score | Standard Deviation 12.126 |
| Double-Blind Treatment Period - Part A: Placebo | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Pain Interference | -1.53 t-score | Standard Deviation 6.257 |
| Double-Blind Treatment Period - Part A: Placebo | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Physical Function | 1.53 t-score | Standard Deviation 2.207 |
| Double-Blind Treatment Period - Part A: Soticlestat | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Pain Interference | -0.38 t-score | Standard Deviation 7.597 |
| Double-Blind Treatment Period - Part A: Soticlestat | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Physical Function | 2.39 t-score | Standard Deviation 4.042 |
| Double-Blind Treatment Period - Part A: Soticlestat | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Anxiety | -1.99 t-score | Standard Deviation 9.567 |
| Double-Blind Treatment Period - Part A: Soticlestat | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Depression | -0.78 t-score | Standard Deviation 6.902 |
| Double-Blind Treatment Period - Part A: Soticlestat | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Fatigue | -3.66 t-score | Standard Deviation 10.456 |
| Double-Blind Treatment Period - Part A: Soticlestat | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Sleep Disturbance | 2.55 t-score | Standard Deviation 1.927 |
| Double-Blind Treatment Period - Part A: Soticlestat | Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Ability to Participate in Social Roles | 2.74 t-score | Standard Deviation 5.147 |
Secondary
Percentage of Participants Considered Responders at the End of Part A
Response was defined as ≥ 30% improvement on the 24-hour pain intensity as assessed by the NPS score. The 24-hour average pain intensity was calculated from current pain intensity scores collected three times a day as measured by the electronic pain diary daily using NPS during Part A. NPS is an 11-point scale, where scores range from 0-10, 0= no pain to 10 = most pain imaginable.
Time frame: Week 15
Population: Full Analysis Set for included all participants who were randomized, received at least 1 dose of study drug, and had at least one valid post-baseline value for the assessment of average 24-hour pain score. The data is reported for Part A in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Treatment Period - Part A: Placebo | Percentage of Participants Considered Responders at the End of Part A | 22.2 percentage of participants |
| Double-Blind Treatment Period - Part A: Soticlestat | Percentage of Participants Considered Responders at the End of Part A | 26.7 percentage of participants |
Secondary
Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A
The PGIC is a 7-point Likert scale to address the following question: Since beginning treatment at this clinic would you describe any changes (if any) in activity, limitations, symptoms, emotions and overall quality of life related to your painful condition compared to before treatment? Participants select from scale range of 1-7: very much improved (1); much improved (2); minimally improved (3); no change (4); minimally worse (5); much worse (6); very much worse (7). Only categories with at least 1 participant were reported.
Time frame: Week 15
Population: Full Analysis Set for included all participants who were randomized, received at least 1 dose of study drug, and had at least one valid post-baseline value for the assessment of average 24-hour pain score. The data is reported for Part A in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Treatment Period - Part A: Placebo | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | Minimally Improved | 11.1 percentage of participants |
| Double-Blind Treatment Period - Part A: Placebo | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | Minimally Worse | 11.1 percentage of participants |
| Double-Blind Treatment Period - Part A: Placebo | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | No Change | 22.2 percentage of participants |
| Double-Blind Treatment Period - Part A: Placebo | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | Missing | 22.2 percentage of participants |
| Double-Blind Treatment Period - Part A: Placebo | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | Much Improved | 33.3 percentage of participants |
| Double-Blind Treatment Period - Part A: Soticlestat | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | Missing | 20.0 percentage of participants |
| Double-Blind Treatment Period - Part A: Soticlestat | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | Much Improved | 33.3 percentage of participants |
| Double-Blind Treatment Period - Part A: Soticlestat | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | Minimally Improved | 13.3 percentage of participants |
| Double-Blind Treatment Period - Part A: Soticlestat | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | No Change | 33.3 percentage of participants |
| Double-Blind Treatment Period - Part A: Soticlestat | Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A | Minimally Worse | 0 percentage of participants |
Secondary
Percent Change From Baseline in CSS at the End of Part A
Signs and symptoms reflecting the sensory, vasomotor, sudomotor/edema, and motor/trophic disturbances of CRPS had been incorporated into a clinically feasible CSS. Total CSS is a 16-point score which was calculated by the number of yes answers to the questions on the 8 symptoms and 8 signs when all 16 questions were answered. Negative percent change from Baseline indicates improvement.
Time frame: Baseline and Week 15
Population: Full Analysis Set for included all participants who were randomized, received at least 1 dose of study drug, and had at least one valid post-baseline value for the assessment of average 24-hour pain score. The data is reported for Part A in this outcome measure. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Treatment Period - Part A: Placebo | Percent Change From Baseline in CSS at the End of Part A | -16.1 percent change | Standard Deviation 18.89 |
| Double-Blind Treatment Period - Part A: Soticlestat | Percent Change From Baseline in CSS at the End of Part A | -23.8 percent change | Standard Deviation 26.29 |
Secondary
Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A
PROMIS-29 (v2.1) is a health-related quality of life survey assessing 7 domains with 4 questions on a 5-point Likert scale. Total raw domain scores are converted into T-scores from a reference population: Depression: 1=never to 5=always, T-scores:41.0-79.4; Physical function: 1=unable to do to 5=without any difficulty, T-scores: 22.5-57.0; Anxiety: 1=never to 5=always, T-scores: 40.3-81.6; Pain interference: 1=not at all to 5=very much, T-scores: 41.6-75.6; Fatigue: 1=not at all to 5=very much, T-scores: 33.7-75.8; Sleep disturbance: 1=very much to 5=not at all, T-scores: 32.0-73.3; Ability to participate in social roles or activities: 1=always to 5=never, T-scores: 27.5-64.2. High scores signify more of domain being measured. Thus, on symptom-oriented domains, higher scores=worse symptomatology and a negative change from Baseline indicates improvement. On function-oriented domains, higher score=better functioning and a positive change from Baseline indicates improvement.
Time frame: Baseline and Week 15
Population: Full Analysis Set for included all participants who were randomized, received at least 1 dose of study drug, and had at least one valid post-baseline value for the assessment of average 24-hour pain score. The data is reported for Part A in this outcome measure. Number analyzed are the number of participants with data available for analyses in the given category (domain).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Treatment Period - Part A: Placebo | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Depression | 4.51 percent change | Standard Deviation 21.864 |
| Double-Blind Treatment Period - Part A: Placebo | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Sleep Disturbance | 4.46 percent change | Standard Deviation 9.611 |
| Double-Blind Treatment Period - Part A: Placebo | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Anxiety | 9.35 percent change | Standard Deviation 24.153 |
| Double-Blind Treatment Period - Part A: Placebo | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Ability to Participate in Social Roles | 4.39 percent change | Standard Deviation 15.195 |
| Double-Blind Treatment Period - Part A: Placebo | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Fatigue | 2.42 percent change | Standard Deviation 22.902 |
| Double-Blind Treatment Period - Part A: Placebo | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Pain Interference | -1.88 percent change | Standard Deviation 9.149 |
| Double-Blind Treatment Period - Part A: Placebo | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Physical Function | 4.27 percent change | Standard Deviation 6.197 |
| Double-Blind Treatment Period - Part A: Soticlestat | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Pain Interference | 0.82 percent change | Standard Deviation 15.571 |
| Double-Blind Treatment Period - Part A: Soticlestat | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Physical Function | 8.00 percent change | Standard Deviation 14.106 |
| Double-Blind Treatment Period - Part A: Soticlestat | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Anxiety | -2.43 percent change | Standard Deviation 16.584 |
| Double-Blind Treatment Period - Part A: Soticlestat | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Depression | 0.04 percent change | Standard Deviation 13.494 |
| Double-Blind Treatment Period - Part A: Soticlestat | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Fatigue | -4.62 percent change | Standard Deviation 16.045 |
| Double-Blind Treatment Period - Part A: Soticlestat | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Sleep Disturbance | 4.75 percent change | Standard Deviation 3.6 |
| Double-Blind Treatment Period - Part A: Soticlestat | Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A | Ability to Participate in Social Roles | 7.42 percent change | Standard Deviation 13.796 |
Secondary
Percent Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A
The 24-hour average pain intensity was calculated from current pain intensity scores collected three times a day as measured by the electronic pain diary daily using NPS. NPS is an 11-point scale, where scores range from 0-10, 0= no pain to 10 = most pain imaginable. Negative percent change from Baseline indicated improvement.
Time frame: Baseline and Week 15
Population: Full Analysis Set for included all participants who were randomized, received at least 1 dose of study drug, and had at least one valid post-baseline value for the assessment of average 24-hour pain score. The data is reported for Part A in this outcome measure. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Treatment Period - Part A: Placebo | Percent Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A | -12.20 percent change | Standard Deviation 29.108 |
| Double-Blind Treatment Period - Part A: Soticlestat | Percent Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A | -18.35 percent change | Standard Deviation 23.699 |