Trial Outcomes & Findings for A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome (NCT NCT02829268)
NCT ID: NCT02829268
Last Updated: 2024-03-13
Results Overview
The investigators assess the safety and tolerability of dantrolene sodium administered orally at upper end of therapeutic dose range for 6 months in patients with Wolfram syndrome. More specifically, the investigators perform liver function tests to check the levels of certain enzymes and proteins in participants' blood. Levels that are higher or lower than normal can indicate liver problems. The liver function tests include: Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline Phosphatase (AP), and bilirubin.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
21 participants
Primary outcome timeframe
6 months
Results posted on
2024-03-13
Participant Flow
Participant milestones
| Measure |
Pediatric
Pediatric patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
Adult
Adult patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
13
|
|
Overall Study
COMPLETED
|
8
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome
Baseline characteristics by cohort
| Measure |
Pediatric
n=8 Participants
Pediatric patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
Adult
n=11 Participants
Adult patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
8 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
13 years
n=5 Participants
|
23 years
n=7 Participants
|
18 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
11 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Abnormal liver function test results
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
C-peptide levels in participants during the oral mixed meal tolerance test
|
0.34 ng/mL
STANDARD_DEVIATION 0.07 • n=5 Participants
|
0.19 ng/mL
STANDARD_DEVIATION 0.05 • n=7 Participants
|
0.25 ng/mL
STANDARD_DEVIATION 0.04 • n=5 Participants
|
|
Visual Functioning in participants assessed by Visual Functioning Questionnaire-25
|
68 units on a scale
STANDARD_DEVIATION 2.3 • n=5 Participants
|
74.3 units on a scale
STANDARD_DEVIATION 1.3 • n=7 Participants
|
68.8 units on a scale
STANDARD_DEVIATION 3.1 • n=5 Participants
|
|
Best-corrected visual acuity in participants measured by LogMar Score
|
0.6 LogMAR
STANDARD_DEVIATION 0.2 • n=5 Participants
|
0.8 LogMAR
STANDARD_DEVIATION 0.2 • n=7 Participants
|
0.7 LogMAR
STANDARD_DEVIATION 0.2 • n=5 Participants
|
|
Neurological Functions in participants assessed by the Wolfram Unified Rating Scale (WURS)
|
21.3 score on a scale
STANDARD_DEVIATION 6.4 • n=5 Participants
|
20.5 score on a scale
STANDARD_DEVIATION 2.8 • n=7 Participants
|
20.8 score on a scale
STANDARD_DEVIATION 3.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsThe investigators assess the safety and tolerability of dantrolene sodium administered orally at upper end of therapeutic dose range for 6 months in patients with Wolfram syndrome. More specifically, the investigators perform liver function tests to check the levels of certain enzymes and proteins in participants' blood. Levels that are higher or lower than normal can indicate liver problems. The liver function tests include: Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline Phosphatase (AP), and bilirubin.
Outcome measures
| Measure |
Pediatric
n=8 Participants
Pediatric patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
Adult
n=11 Participants
Adult patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
|---|---|---|
|
Number of Participants With Treatment-related Adverse Events as Assessed by Liver Function Tests
Baseline
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by Liver Function Tests
6 months
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 6 monthsThe investigators determine the effect of dantrolene sodium on residual beta cell functions. The investigators monitor base-line C-peptide levels in participants' blood. The investigators also monitor C-peptide levels in participant's blood during the oral mixed meal tolerance test. The night before the oral mixed meal tolerance test, the participants will turn their insulin pump basal rate to 50% of the normal rate at midnight or take half of their evening dose of Lantus insulin and fasted from midnight until the test at 8 a.m. The mixed meal consists of 6 ml/kg (maximum 360 ml) of Boost Original (Société des Produits Nestlé S.A., Vevey, Switzerland). Blood for glucose and C-peptide measurement will be drawn at time 0 (fasting) and 30 minutes after the Boost. If a subject's fasting glucose exceeds 11.1 mmol/l, the test will not be performed, but fasting glucose and C-peptide will be obtained.
Outcome measures
| Measure |
Pediatric
n=8 Participants
Pediatric patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
Adult
n=11 Participants
Adult patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
|---|---|---|
|
Changes in C-peptide Levels in Participants Assessed by the ELISA Assay
Baseline
|
0.34 ng/mL
Standard Deviation 0.07
|
0.19 ng/mL
Standard Deviation 0.05
|
|
Changes in C-peptide Levels in Participants Assessed by the ELISA Assay
6 months
|
0.47 ng/mL
Standard Deviation 0.13
|
0.30 ng/mL
Standard Deviation 0.09
|
SECONDARY outcome
Timeframe: 6 monthsChanges in Visual Functioning in participants assessed by Visual Functioning Questionnaire-25. The Visual Functioning Questionnaire-25 (VFQ-25) is divided into several subdomains, each assessing a specific aspect of visual functioning and its impact on an individual's life. There are a total of 11 subdomains in the VFQ-25. To calculate the total score on the VFQ-25, we follow these steps: 1. Calculate Subdomain Scores, 2. Weighted Sum 3. Calculate Total Score VFQ-25 provides scores that range from 0 to 100. The total score represents the overall impact of visual functioning on the individual's quality of life, with higher scores indicating better quality of life and less impact from vision problems.
Outcome measures
| Measure |
Pediatric
n=8 Participants
Pediatric patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
Adult
n=11 Participants
Adult patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
|---|---|---|
|
Changes in Visual Functioning in Participants Assessed by Visual Functioning Questionnaire-25.
Baseline
|
68 units on a scale
Standard Error 2.3
|
74.3 units on a scale
Standard Error 1.3
|
|
Changes in Visual Functioning in Participants Assessed by Visual Functioning Questionnaire-25.
6 months
|
70.5 units on a scale
Standard Error 2.9
|
73.5 units on a scale
Standard Error 2.4
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Patient 012 was excluded from analysis due to LogMar of 3 (No Light Perception)
Best-corrected visual acuity is assessed using the Snellen optotype and then converted into LogMar Scores (Minimum: -0.30, Maximum: 3.0). A higher LogMar score signifies poorer vision.
Outcome measures
| Measure |
Pediatric
n=8 Participants
Pediatric patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
Adult
n=10 Participants
Adult patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
|---|---|---|
|
Changes in Best-corrected Visual Acuity in Participants Measured by LogMar Score
Baseline
|
0.6 LogMAR
Standard Error 0.2
|
0.8 LogMAR
Standard Error 0.2
|
|
Changes in Best-corrected Visual Acuity in Participants Measured by LogMar Score
6 months
|
0.6 LogMAR
Standard Error 0.2
|
0.9 LogMAR
Standard Error 0.2
|
SECONDARY outcome
Timeframe: 6 monthsNeurological functions are assessed by the Wolfram Unified Rating Scale (WURS). The WURS is divided into the following subscales: Physical Assessment and Behavioral Assessment. Physical Assessment (34 items rated on a scale from 0 = no symptoms to 4 = highest severity, minimum: 0, Maximum: 136) and Behavioral Assessment (9 items rated on frequency and severity from 0 = normal behavior to 3 = highest severity, Minimum: 0, Maximum: 27). Subscale scores are summed to calculate the total scores (minimum: 0, Maximum: 163). Higher total scores indicate more severe neurological manifestations.
Outcome measures
| Measure |
Pediatric
n=8 Participants
Pediatric patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
Adult
n=11 Participants
Adult patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period with an optional extension phase up to 24 months, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
|---|---|---|
|
Changes in Neurological Functions in Participants Assessed by the Wolfram Unified Rating Scale (WURS)
Baseline
|
21.3 score on a scale
Standard Error 6.4
|
20.5 score on a scale
Standard Error 2.8
|
|
Changes in Neurological Functions in Participants Assessed by the Wolfram Unified Rating Scale (WURS)
6 months
|
18.4 score on a scale
Standard Error 5.7
|
18.6 score on a scale
Standard Error 4.5
|
Adverse Events
Pediatric
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Adult
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Pediatric
n=8 participants at risk
Pediatric patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
Adult
n=11 participants at risk
Adult patients treated with dantrolene sodium
dantrolene sodium: The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.
There is a screening period up to 56 days, a 6-month treatment period, and a 4-week safety follow-up period. Study assessments include medical \& medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
2/8 • 6 months
|
27.3%
3/11 • 6 months
|
|
Nervous system disorders
Weakness
|
37.5%
3/8 • 6 months
|
9.1%
1/11 • 6 months
|
|
Nervous system disorders
Dizziness
|
25.0%
2/8 • 6 months
|
9.1%
1/11 • 6 months
|
|
Hepatobiliary disorders
Elevated Hepatic enzymes
|
0.00%
0/8 • 6 months
|
18.2%
2/11 • 6 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/8 • 6 months
|
18.2%
2/11 • 6 months
|
|
Gastrointestinal disorders
Gastrointestinal upset
|
12.5%
1/8 • 6 months
|
9.1%
1/11 • 6 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.5%
1/8 • 6 months
|
9.1%
1/11 • 6 months
|
|
Endocrine disorders
Hypoglycemia (mild)
|
37.5%
3/8 • 6 months
|
36.4%
4/11 • 6 months
|
|
Nervous system disorders
Headaches
|
25.0%
2/8 • 6 months
|
36.4%
4/11 • 6 months
|
|
Renal and urinary disorders
hyponatremia
|
12.5%
1/8 • 6 months
|
27.3%
3/11 • 6 months
|
|
Endocrine disorders
Hyperglycemia
|
25.0%
2/8 • 6 months
|
9.1%
1/11 • 6 months
|
|
Renal and urinary disorders
Urinary Tract Infection
|
12.5%
1/8 • 6 months
|
27.3%
3/11 • 6 months
|
|
Renal and urinary disorders
Hyperkalemia
|
12.5%
1/8 • 6 months
|
0.00%
0/11 • 6 months
|
|
Renal and urinary disorders
Urinary Retention
|
12.5%
1/8 • 6 months
|
0.00%
0/11 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Influenza
|
12.5%
1/8 • 6 months
|
9.1%
1/11 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinovirus infection
|
12.5%
1/8 • 6 months
|
0.00%
0/11 • 6 months
|
|
Infections and infestations
Knee Infection
|
12.5%
1/8 • 6 months
|
0.00%
0/11 • 6 months
|
|
Nervous system disorders
Tics
|
12.5%
1/8 • 6 months
|
0.00%
0/11 • 6 months
|
|
Skin and subcutaneous tissue disorders
Knee Effusions
|
12.5%
1/8 • 6 months
|
0.00%
0/11 • 6 months
|
|
Injury, poisoning and procedural complications
Hit by car
|
0.00%
0/8 • 6 months
|
9.1%
1/11 • 6 months
|
|
Nervous system disorders
Fatigue
|
37.5%
3/8 • 6 months
|
45.5%
5/11 • 6 months
|
Additional Information
Fumihiko Urano, MD, PhD
Washington University School of Medicine, Department of Medicine, Division of Endocrinology
Phone: 314-362-8683
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place