CClinicalTrials.gg
CompletedNCT04662281RELIEF-PHN1Updated Feb 13, 2026Results posted

Efficacy and Safety of LX9211 in Participants With Postherpetic Neuralgia

A Phase 2 interventional study of Placebo and LX9211 in Postherpetic Neuralgia, sponsored by Lexicon Pharmaceuticals. Completed at 32 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-13.

Sponsored by Lexicon Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
79
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Evaluation of the efficacy of LX9211 compared to placebo in reducing pain related to postherpetic neuralgia over an 11 week assessment period.

02

Conditions studied

  • Postherpetic Neuralgia
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Participant has given written informed consent to participate in the study in accordance with local regulations
  • Adult male and female participants ≥18 years of age at the time of screening
  • Postherpetic neuralgia (PHN) pain that is present for ≥3 months after healing of herpes zoster skin rash affecting a single dermatome (Participants with more than 1 involved dermatome may also be included, provided the affected dermatomes are contiguous)
  • Moderate to severe pain as confirmed by average pain score using scores recorded in the pain diary in the 14 days prior to randomization

Exclusion criteria

Exclusion Criteria:

  • Presence of other painful conditions that may confound assessment or self-evaluation of PHN
  • History of major depressive episode, active, significant psychiatric disorders
  • History of clinically significant drug or alcohol use disorder
  • PHN affecting the face
  • Use of opioid medications for management of PHN within the 2 months prior to Screening Visit
  • Use of Non-steroidal anti-inflammatory drugs (NSAIDs) for the specific treatment of PHN pain
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
79 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Following a 2-week Single-blind Run-in period, participants will receive a single loading dose of matching-placebo to LX9211 tablet, orally, on Day 1 and maintenance doses, orally, once daily from Day 2 to Week 6.

    Drug: Placebo

  • Experimental
    LX9211

    Following a 2-week Single-blind Run-in period, participants will receive a single loading dose of 200 milligrams (mg) tablet, orally, on Day 1 and maintenance doses of 20 mg, orally, once daily from Day 2 to Week 6.

    Drug: LX9211

Interventions

  • DrugPlacebo

    LX9211 matching-placebo, tablets will be administered orally.

  • DrugLX9211

    LX9211 tablets will be administered orally.

05

What researchers measure

Primary outcomes

  1. Change From Baseline (Week 2 of the Run-in Period) in Average Daily Pain Score (ADPS)

    ADPS is based on question 5 of Zoster Brief Pain Inventory (ZBPI) and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine. Higher ADPS scores indicates a worse outcome. Negative change from baseline indicates no pain.

    Time frame: Baseline (Week 2 of the Run-in period) to Week 6

Secondary outcomes

  1. Change From Baseline in Pain Interfering With Sleep Based on Question 9F of the ZBPI at Week 6

    Pain interfering with sleep is based on Question 9F of the ZBPI "Indicate the one number that describes how, in the past 24-hours shingles pain has interfered with your: Sleep; 0 = does not interfere to 10 = Completely interferes. Higher the number, the worsening of sleep due to pain interference. Negative change from baseline indicates no interference in sleep. Pain interfering with sleep was based on the daily pain diary data based on Q 9F of the ZBPI.

    Time frame: Baseline to Week 6

  2. Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline at Week 6

    ADPS is based on question 5 of Zoster Brief Pain Inventory (ZBPI) and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine. Higher ADPS scores indicated a worse outcome.

    Time frame: Baseline to Week 6

  3. Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6

    ADPS is based on question 5 of ZBPI and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine. Higher ADPS scores indicated a worse outcome.

    Time frame: Baseline to Week 6

  4. Change From Baseline in Interference in General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life Interference Based on the Questions 9A-G of the ZBPI

    The ZBPI, a 9-item questionnaire, assesses the severity of pain and its impact on functioning in participants with postherpetic neuralgia (PHN). Each question concerning daily activity (General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life) was scored on a scale from 0 to 10, where 0 indicated no interference and 10 indicated complete interference. Higher ZBPI score indicates a worse outcome. Negative change from baseline indicates no interference in all daily activities. The pain interference at Week 6 in this outcome measure was based on data collected on the ZBPI administered at the Week 6 in-person clinic visit.

    Time frame: Baseline to Week 6

  5. Number of Participants Discontinuing Treatment Due to Lack of Efficacy Defined as Increase in ADPS From Baseline of ≥30% Based on Question 5 of the ZBPI

    ADPS is based on question 5 of ZBPI and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine.

    Time frame: Baseline to Week 6

  6. Patient Global Impression of Change (PGIC) at Week 6

    PGIC is assessed on a 7-point rating scale where 1= very much improved to 7 = very much worse. Higher scores indicate worse outcomes.

    Time frame: Baseline to Week 6

  7. Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving ≥30% Reduction in Pain Intensity in ADPS Based on Question 5 of the ZBPI.

    ADPS is based on question 5 of ZBPI and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine.

    Time frame: Week 6 to Week 11

  8. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Adverse Events (AEs) are defined as any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs are defined as any AEs reported after the first dose of double-blind study medication on study Day 1.

    Time frame: From first dose of study drug up to end of double-blind treatment period (up to Week 6) and end of single-blind treatment period (up to Week 11)

06

Results

Posted Feb 13, 2026

Participant flow

Participants took part in the study at multiple investigative sites from 10 Dec 2020 to 28 Dec 2022.

Participant flow — Overall Study
MilestonePlaceboLX9211
Started4138
Completed3421
Not completed717
Withdrew: Adverse event413
Withdrew: Withdrawal by subject12
Withdrew: Lack of efficacy10
Withdrew: Reason not specified12

Outcome measures

PrimaryChange From Baseline (Week 2 of the Run-in Period) in Average Daily Pain Score (ADPS)

ADPS is based on question 5 of Zoster Brief Pain Inventory (ZBPI) and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine. Higher ADPS scores indicates a worse outcome. Negative change from baseline indicates no pain.

Time frame:
Baseline (Week 2 of the Run-in period) to Week 6
Reported as:
Least squares mean · score on a scale
Change From Baseline (Week 2 of the Run-in Period) in Average Daily Pain Score (ADPS)
score on a scalePlaceboLX9211
Change From Baseline (Week 2 of the Run-in Period) in Average Daily Pain Score (ADPS)-1.62 ± 0.360-2.42 ± 0.397
Statistical analysis
  • Placebo vs LX9211 · MMRM · p = 0.120 · Difference in least squares means: -0.80 · 95% CI -1.82 to 0.21
SecondaryChange From Baseline in Pain Interfering With Sleep Based on Question 9F of the ZBPI at Week 6

Pain interfering with sleep is based on Question 9F of the ZBPI "Indicate the one number that describes how, in the past 24-hours shingles pain has interfered with your: Sleep; 0 = does not interfere to 10 = Completely interferes. Higher the number, the worsening of sleep due to pain interference. Negative change from baseline indicates no interference in sleep. Pain interfering with sleep was based on the daily pain diary data based on Q 9F of the ZBPI.

Time frame:
Baseline to Week 6
Reported as:
Least squares mean · score on a scale
Change From Baseline in Pain Interfering With Sleep Based on Question 9F of the ZBPI at Week 6
score on a scalePlaceboLX9211
Change From Baseline in Pain Interfering With Sleep Based on Question 9F of the ZBPI at Week 6-1.43 ± 0.323-2.04 ± 0.364
Statistical analysis
  • Placebo vs LX9211 · MMRM · p = 0.181 · Difference in least squares means: -0.62 · 95% CI -1.53 to 0.29
SecondaryPercentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline at Week 6

ADPS is based on question 5 of Zoster Brief Pain Inventory (ZBPI) and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine. Higher ADPS scores indicated a worse outcome.

Time frame:
Baseline to Week 6
Reported as:
Number · percentage of participants
Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline at Week 6
percentage of participantsPlaceboLX9211
Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline at Week 634.1542.11
Statistical analysis
  • Placebo vs LX9211 · Cochran-Mantel-Haenszel · p = 0.504 · Percentage difference: 8.0 · 95% CI -13.42 to 29.34
SecondaryPercentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6

ADPS is based on question 5 of ZBPI and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine. Higher ADPS scores indicated a worse outcome.

Time frame:
Baseline to Week 6
Reported as:
Number · percentage of participants
Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6
percentage of participantsPlaceboLX9211
Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 619.5123.68
Statistical analysis
  • Placebo vs LX9211 · Cochran-Mantel-Haenszel · p = 0.671 · Percentage difference: 4.2 · 95% CI -13.99 to 22.33
SecondaryChange From Baseline in Interference in General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life Interference Based on the Questions 9A-G of the ZBPI

The ZBPI, a 9-item questionnaire, assesses the severity of pain and its impact on functioning in participants with postherpetic neuralgia (PHN). Each question concerning daily activity (General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life) was scored on a scale from 0 to 10, where 0 indicated no interference and 10 indicated complete interference. Higher ZBPI score indicates a worse outcome. Negative change from baseline indicates no interference in all daily activities. The pain interference at Week 6 in this outcome measure was based on data collected on the ZBPI administered at the Week 6 in-person clinic visit.

Time frame:
Baseline to Week 6
Reported as:
Least squares mean · score on a scale
Change From Baseline in Interference in General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life Interference Based on the Questions 9A-G of the ZBPI
score on a scalePlaceboLX9211
General Activity: Change at Week 6-0.52 ± 0.392-1.75 ± 0.417
Mood: Change at Week 6-1.52 ± 0.407-2.36 ± 0.435
Walking Ability: Change at Week 6-0.28 ± 0.373-0.72 ± 0.391
Normal Work: Change at Week 6-0.61 ± 0.383-1.28 ± 0.397
Relations With Other People: Change at Week 6-0.89 ± 0.381-1.27 ± 0.400
Relations With Sleep: Change at Week 6-1.61 ± 0.370-1.66 ± 0.382
Enjoyment of Life: Change at Week 6-1.13 ± 0.405-1.93 ± 0.435
Statistical analysis
  • Placebo vs LX9211 · MMRM · p = 0.024 · Difference in least squares means: -1.23 · 95% CI -2.30 to -0.17
  • Placebo vs LX9211 · MMRM · p = 0.138 · Difference in least squares means: -0.84 · 95% CI -1.95 to 0.27
  • Placebo vs LX9211 · MMRM · p = 0.397 · Difference in least squares means: -0.43 · 95% CI -1.45 to 0.58
  • Placebo vs LX9211 · MMRM · p = 0.192 · Difference in least squares means: -0.67 · 95% CI -1.69 to 0.34
  • Placebo vs LX9211 · MMRM · p = 0.463 · Difference in least squares means: -0.38 · 95% CI -1.41 to 0.65
  • Placebo vs LX9211 · MMRM · p = 0.908 · Difference in least squares means: -0.06 · 95% CI -1.05 to 0.93
  • Placebo vs LX9211 · MMRM · p = 0.158 · Difference in least squares means: -0.79 · 95% CI -1.90 to 0.31
SecondaryNumber of Participants Discontinuing Treatment Due to Lack of Efficacy Defined as Increase in ADPS From Baseline of ≥30% Based on Question 5 of the ZBPI

ADPS is based on question 5 of ZBPI and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine.

Time frame:
Baseline to Week 6
Reported as:
Count of participants · Participants
Number of Participants Discontinuing Treatment Due to Lack of Efficacy Defined as Increase in ADPS From Baseline of ≥30% Based on Question 5 of the ZBPI
ParticipantsPlaceboLX9211
Number of Participants Discontinuing Treatment Due to Lack of Efficacy Defined as Increase in ADPS From Baseline of ≥30% Based on Question 5 of the ZBPI10
SecondaryPatient Global Impression of Change (PGIC) at Week 6

PGIC is assessed on a 7-point rating scale where 1= very much improved to 7 = very much worse. Higher scores indicate worse outcomes.

Time frame:
Baseline to Week 6
Reported as:
Least squares mean · score on a scale
Patient Global Impression of Change (PGIC) at Week 6
score on a scalePlaceboLX9211
Patient Global Impression of Change (PGIC) at Week 63.06 ± 0.2222.65 ± 0.265
Statistical analysis
  • Placebo vs LX9211 · ANOVA · p = 0.192 · Difference in least squares means: -0.42 · 95% CI -1.05 to 0.22
SecondaryTime to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving ≥30% Reduction in Pain Intensity in ADPS Based on Question 5 of the ZBPI.

ADPS is based on question 5 of ZBPI and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine.

Time frame:
Week 6 to Week 11
Reported as:
Median · weeks
Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving ≥30% Reduction in Pain Intensity in ADPS Based on Question 5 of the ZBPI.
weeksPlaceboLX9211
Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving ≥30% Reduction in Pain Intensity in ADPS Based on Question 5 of the ZBPI.NA (NA to NA)NA (NA to NA)
SecondaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs)

Adverse Events (AEs) are defined as any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs are defined as any AEs reported after the first dose of double-blind study medication on study Day 1.

Time frame:
From first dose of study drug up to end of double-blind treatment period (up to Week 6) and end of single-blind treatment period (up to Week 11)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
ParticipantsPlacebo (Double-blind Treatment Period)LX9211 (Double-blind Treatment Period)Placebo (Single-blind Placebo Safety Follow-up Period)LX9211 (Single-blind Placebo Safety Follow-up Period)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)132495

Adverse events

Collected over From first dose of study drug up to end of double-blind treatment period (up to Week 6) and end of single-blind treatment period (up to Week 11). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo (Double-blind Treatment Period)0/41 (0%)0/41 (0%)6/41 (14.6%)
LX9211 (Double-blind Treatment Period)0/38 (0%)0/38 (0%)24/38 (63.2%)
Placebo (Single-blind Placebo Safety Follow-up Period)0/38 (0%)0/38 (0%)2/38 (5.3%)
LX9211 (Single-blind Placebo Safety Follow-up Period)0/31 (0%)0/31 (0%)1/31 (3.2%)
Most frequent other events
Most frequent other events
EventPlacebo (Double-blind Treatment Period)LX9211 (Double-blind Treatment Period)Placebo (Single-blind Placebo Safety Follow-up Period)LX9211 (Single-blind Placebo Safety Follow-up Period)
DizzinessNervous system disorders2/4111/380/380/31
ConstipationGastrointestinal disorders0/414/380/380/31
HeadacheNervous system disorders2/414/381/381/31
NauseaGastrointestinal disorders0/413/380/381/31
Urinary tract infectionInfections and infestations2/413/382/381/31
DiarrheaGastrointestinal disorders3/410/380/380/31
VertigoEar and labyrinth disorders0/412/380/380/31
Dry mouthGastrointestinal disorders0/412/380/380/31
Balance disorderNervous system disorders0/412/380/380/31
SomnolenceNervous system disorders0/412/380/380/31

Baseline characteristics

Modified Intent-to-Treat (mITT) population included all randomized participants who had taken at least 1 dose of study drug.

Age, Continuous
Age, Continuous(years)PlaceboLX9211Total
Mean63.6 ± 12.565.4 ± 11.764.5 ± 12.1
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboLX9211Total
Female242347
Male171532
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboLX9211Total
Hispanic or Latino121123
Not Hispanic or Latino292756
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboLX9211Total
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American202
White393776
More than one race000
Unknown or Not Reported011
07

Study locations

32 sites
  • Lexicon Investigational Site
    Scottsdale, Arizona 85258, United States
  • Lexicon Investigational Site
    Tucson, Arizona 85741, United States
  • Lexicon Investigational Site
    Greenbrae, California 94904, United States
  • Lexicon Investigational Site
    Brandon, Florida 33511, United States
  • Lexicon Investigational Site (113)
    Miami, Florida 33032, United States
  • Lexicon Investigational Site
    Miami, Florida 33144, United States
  • Lexicon Investigational Site
    Miami, Florida 33174, United States
  • Lexicon Investigational Site
    Ormond Beach, Florida 32174, United States
  • Lexicon Investigational Site
    Winter Park, Florida 32789, United States
  • Lexicon Investigational Site (147)
    Marietta, Georgia 30060, United States
  • Lexicon Investigational Site
    Flossmoor, Illinois 60422, United States
  • Lexicon Investigational Site
    Wauconda, Illinois 60084, United States
  • Lexicon Investigational Site
    Boston, Massachusetts 02131, United States
  • Lexicon Investigational Site
    Canton, Michigan 48187, United States
  • Lexicon Investigational Site
    Hazelwood, Missouri 63042, United States
  • Lexicon Investigational Site
    Albuquerque, New Mexico 87102, United States
  • Lexicon Investigational Site (148)
    Cary, North Carolina 27518, United States
  • Lexicon Investigational Site
    Jenkintown, Pennsylvania 19046, United States
  • Lexicon Investigational Site
    Baytown, Texas 77521, United States
  • Lexicon Investigational Site
    Victoria, Texas 77901, United States
  • Lexicon Investigational Site
    Salt Lake City, Utah 84102, United States
  • Lexicon Investigational Site
    Kenosha, Wisconsin 53144, United States
  • Lexicon Investigational Site (138)
    Choceň, 565 01, Czechia
  • Lexicon Investigational Site (140)
    Pardubice, 53002, Czechia
  • Lexicon Investigational Site (136)
    Prague, 100 00 00, Czechia
  • Lexicon Investigational Site (137)
    Prague, 12000, Czechia
  • Lexicon Investigational Site (141)
    Prague, 13000, Czechia
  • Lexicon Investigational Site (135)
    Prague, 16000, Czechia
  • Lexicon Investigational Site (128)
    Katowice, 40-282, Poland
  • Lexicon Investigational Site (130)
    Katowice, 640-748, Poland
  • Lexicon Investigational Site (134)
    Lublin, 20-064, Poland
  • Lexicon Investigational Site (133)
    Warsaw, 01-868, Poland
08

References and documents

Publications

  • Luo G, Chen L, Kostich WA, Hamman B, Allen J, Easton A, Bourin C, Gulianello M, Lippy J, Nara S, Maishal TK, Thiyagarajan K, Jalagam P, Pattipati SN, Dandapani K, Dokania M, Vattikundala P, Sharma V, Elavazhagan S, Verma MK, Das ML, Wagh S, Balakrishnan A, Johnson BM, Santone KS, Thalody G, Denton R, Saminathan H, Holenarsipur VK, Kumar A, Rao A, Putlur SP, Sarvasiddhi SK, Shankar G, Louis JV, Ramarao M, Conway CM, Li YW, Pieschl R, Tian Y, Hong Y, Ditta J, Mathur A, Li J, Smith D, Pawluczyk J, Sun D, Yip S, Wu DR, Vetrichelvan M, Gupta A, Wilson A, Gopinathan S, Wason S, Bristow L, Albright CF, Bronson JJ, Macor JE, Dzierba CD. Discovery of (S)-1-((2',6-Bis(difluoromethyl)-[2,4'-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine (BMS-986176/LX-9211): A Highly Selective, CNS Penetrable, and Orally Active Adaptor Protein-2 Associated Kinase 1 Inhibitor in Clinical Trials for the Treatment of Neuropathic Pain. J Med Chem. 2022 Mar 24;65(6):4457-4480. doi: 10.1021/acs.jmedchem.1c02131. Epub 2022 Mar 8. PubMed 35257579 ↗

Study documents

  • Study protocol · Oct 18, 2021
  • Statistical analysis plan · Nov 28, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants.

Supporting information: Study protocol, Sap, Csr

09

Registry details

Key details

Study ID
NCT04662281
Lead sponsor
Lexicon Pharmaceuticals
Responsible party
Sponsor
First posted
Dec 10, 2020
Start date
Dec 10, 2020
Primary completion
Nov 18, 2022
Completion
Dec 28, 2022
Results posted
Feb 13, 2026
Last update
Feb 13, 2026

Study contacts

Suma Gopinathan, PhD
study director · Lexicon Pharmaceuticals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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