Trial Outcomes & Findings for Long Term Treatment of Herpes Simplex Encephalitis (HSE) With Valacyclovir (NCT NCT00031486)
NCT ID: NCT00031486
Last Updated: 2012-06-12
Results Overview
Number of subjects who were assessed to have no or mild neuropsychological impairment at 12 months using the Mattis Dementia Rating Scale. (A score of 121 or higher refects no or mild neuropsychological impairment.) Scale is: 139-144 normal; 121-139 mild; 114-120 moderate; 87-113 severe; and \<=86 very severe.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
91 participants
Primary outcome timeframe
One year post therapy.
Results posted on
2012-06-12
Participant Flow
Subjects enrolled in the study presented with findings of HSE.
Patients considered for enrollment are those who are receiving and will have completed IV Acyclovir for a minimum duration of 14 days to a maximum of 21 days at a minimum dose of 30 mg/kg/day to a maximum dose of 60 mg/kg/day.
Participant milestones
| Measure |
Valacyclovir
four 500 mg tablets 3 times a day for 90 days
|
Placebo
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
|---|---|---|
|
Overall Study
STARTED
|
40
|
47
|
|
Overall Study
COMPLETED
|
33
|
35
|
|
Overall Study
NOT COMPLETED
|
7
|
12
|
Reasons for withdrawal
| Measure |
Valacyclovir
four 500 mg tablets 3 times a day for 90 days
|
Placebo
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Death
|
0
|
3
|
|
Overall Study
Non-compliant
|
0
|
4
|
|
Overall Study
Did not meet eligibility requirement
|
2
|
1
|
|
Overall Study
Other
|
1
|
1
|
Baseline Characteristics
Long Term Treatment of Herpes Simplex Encephalitis (HSE) With Valacyclovir
Baseline characteristics by cohort
| Measure |
Valacyclovir
n=40 Participants
four 500 mg tablets 3 times a day for 90 days
|
Placebo
n=47 Participants
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
Total
n=87 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
53.5 years
n=5 Participants
|
56 years
n=7 Participants
|
55 years
n=5 Participants
|
|
Age, Customized
12-18 years
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Age, Customized
19-40 years
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Age, Customized
41-60 years
|
18 participants
n=5 Participants
|
22 participants
n=7 Participants
|
40 participants
n=5 Participants
|
|
Age, Customized
61 years or older
|
13 participants
n=5 Participants
|
20 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
9 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
6 participants
n=5 Participants
|
4 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
26 participants
n=5 Participants
|
31 participants
n=7 Participants
|
57 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: One year post therapy.Population: All subjects that survived to 12 months and were assessed.
Number of subjects who were assessed to have no or mild neuropsychological impairment at 12 months using the Mattis Dementia Rating Scale. (A score of 121 or higher refects no or mild neuropsychological impairment.) Scale is: 139-144 normal; 121-139 mild; 114-120 moderate; 87-113 severe; and \<=86 very severe.
Outcome measures
| Measure |
Valacyclovir
n=33 Participants
four 500 mg tablets taken 3 times a day for 90 days
|
Placebo
n=36 Participants
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
Total
n=62 Participants
|
|---|---|---|---|
|
Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS)
MDRS score < 121 (negative)
|
5 Participants
|
2 Participants
|
7 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS)
MDRS Score >= 121 (positive)
|
28 Participants
|
34 Participants
|
62 Participants
|
SECONDARY outcome
Timeframe: Day 0 and 90, Day 0 and Month 6 and Day 0 and Month 12Population: All subjects that were assessed at baseline and the following time points: 90 days, 6 and 12 months.
The SF-36 Questionnaire measures quality of life as reported by the subject. The questionnaire contains 36 questions, each questions can be assigned a maximum score of 100. For each subject, a perfect score would be 3600, hence the higher score is best. The calculated scores reported in the table below reflect the diffence between Day 0 (day study drug started) and Day 90, Day 0 (day study drug started) and Month 6, and Day 0 (day study drug started) and Month 12.
Outcome measures
| Measure |
Valacyclovir
n=28 Participants
four 500 mg tablets taken 3 times a day for 90 days
|
Placebo
n=33 Participants
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
Total
n=61 Participants
|
|---|---|---|---|
|
Effect of Study Medication on Quality of Life Measurements.
SF-36 score difference from day 0 to 90
|
465 Scores on a scale Change in SF-36
Interval -745.0 to 2360.0
|
307.5 Scores on a scale Change in SF-36
Interval -935.0 to 2575.0
|
355 Scores on a scale Change in SF-36
Interval -935.0 to 2575.0
|
|
Effect of Study Medication on Quality of Life Measurements.
SF-36 score difference from day 0 to 6 months
|
722.5 Scores on a scale Change in SF-36
Interval -1060.0 to 2125.0
|
475 Scores on a scale Change in SF-36
Interval -1170.0 to 2215.0
|
635 Scores on a scale Change in SF-36
Interval -1170.0 to 2215.0
|
|
Effect of Study Medication on Quality of Life Measurements.
SF-36 score difference from day 0 to 12 months
|
1095 Scores on a scale Change in SF-36
Interval -1565.0 to 2240.0
|
985 Scores on a scale Change in SF-36
Interval -1330.0 to 2355.0
|
985 Scores on a scale Change in SF-36
Interval -1565.0 to 2355.0
|
SECONDARY outcome
Timeframe: Day 0 and Day 90.Population: The number of participants analyzed is 0 because there specimens obtained were inadequate and insufficient to analyze.
Few CSF specimens were collected on day 90, hence unable to calculate the difference in PCR at day 0 and day 90.\[measured quantitatively by polymerase chain reaction (PCR)\].
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 monthsThe measure is the number of adverse events per subject. Adverse events were recorded from time of first dose of study drug through 6 months post start of study drug.
Outcome measures
| Measure |
Valacyclovir
n=36 Participants
four 500 mg tablets taken 3 times a day for 90 days
|
Placebo
n=42 Participants
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
Total
n=78 Participants
|
|---|---|---|---|
|
Median Number of Reported AEs Describing Safety and Tolerance of Valacyclovir (VACV), Evaluated by the Number Adverse Events, Administered at a Dose of 2.0 Grams Given Orally 3 Times a Day for 90 Days.
|
8.5 Events per participants
Interval 1.0 to 25.0
|
8 Events per participants
Interval 1.0 to 38.0
|
8 Events per participants
Interval 1.0 to 38.0
|
SECONDARY outcome
Timeframe: 90 days, 6 and 12 monthsPopulation: All subjects that survived and were assessed at 90 days, 6 and 12 months.
The assessment scoring for the Mattis Dementia Rating Scale is as follows: 139 - 144: no neuropsychological impairment; 121- 138: mild neuropsychological impairment; 114 - 120: moderate neuropsychological impairment; 87 - 113: severe neuropsychological impairment; and \<=86: very severe neuropsychological impairment.
Outcome measures
| Measure |
Valacyclovir
n=31 Participants
four 500 mg tablets taken 3 times a day for 90 days
|
Placebo
n=36 Participants
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
Total
n=67 Participants
|
|---|---|---|---|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Mattis Dementia Rating Scale (MDRS)
MDRS score >= 121 (90 days)
|
28 Participants
|
31 Participants
|
59 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Mattis Dementia Rating Scale (MDRS)
MDRS score < 121 (90 days)
|
3 Participants
|
5 Participants
|
8 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Mattis Dementia Rating Scale (MDRS)
MDRS score >= 121 ( 6 months)
|
24 Participants
|
31 Participants
|
55 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Mattis Dementia Rating Scale (MDRS)
MDRS score < 121 (6 months)
|
5 Participants
|
4 Participants
|
9 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Mattis Dementia Rating Scale (MDRS)
MDRS score >= 121 (12 months)
|
28 Participants
|
34 Participants
|
62 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Mattis Dementia Rating Scale (MDRS)
MDRS score < 121 (12 months)
|
5 Participants
|
2 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: 90 days, 6 and 12 monthsPopulation: All subjects that survived and were assessed at 90 days, 6 and 12 months.
The assessment score for the Mini-Mental Status Examination is as follows: 27 - 30: no neuropsychological impairment; 23 - 26: mild neuropsychological impairment; 16 - 22: moderate neuropsychological impairment; 11 - 15 severe neuropsychological impairment; and \<=10: very severe neuropsychological impairment.
Outcome measures
| Measure |
Valacyclovir
n=29 Participants
four 500 mg tablets taken 3 times a day for 90 days
|
Placebo
n=36 Participants
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
Total
n=65 Participants
|
|---|---|---|---|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days, and at 6 and 12 Months, as Measured by the Mini-Mental Status Examination (MMSE).
MMSE score >= 23 (90 days)
|
26 Participants
|
31 Participants
|
57 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days, and at 6 and 12 Months, as Measured by the Mini-Mental Status Examination (MMSE).
MMSE score < 23 (90 days)
|
3 Participants
|
5 Participants
|
8 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days, and at 6 and 12 Months, as Measured by the Mini-Mental Status Examination (MMSE).
MMSE score >= 23 (6 months)
|
23 Participants
|
29 Participants
|
52 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days, and at 6 and 12 Months, as Measured by the Mini-Mental Status Examination (MMSE).
MMSE score < 23 (6 months)
|
4 Participants
|
4 Participants
|
8 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days, and at 6 and 12 Months, as Measured by the Mini-Mental Status Examination (MMSE).
MMSE score >= 23 (12 months)
|
28 Participants
|
30 Participants
|
58 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days, and at 6 and 12 Months, as Measured by the Mini-Mental Status Examination (MMSE).
MMSE score < 23 (12 months)
|
4 Participants
|
5 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: 90 days, 6 and 12 monthsPopulation: All subjects that survived and were assessed at 90 days, 6 and 12 months.
The assessment scoring for the Glasgow Coma Scale is as follows: 15: no neuropsychological impairment; 12 - 14: mild neuropsychological impairment; 9 - 11: moderate neuropsychological impairment; 6 to 8: severe neuropsychological impairment; and \<6: very severe neuropsychological impairment.
Outcome measures
| Measure |
Valacyclovir
n=33 Participants
four 500 mg tablets taken 3 times a day for 90 days
|
Placebo
n=37 Participants
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
Total
n=70 Participants
|
|---|---|---|---|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS).
GCS score < 12 (90 days)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS).
GCS score >= 12 (6 months)
|
31 Participants
|
36 Participants
|
67 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS).
GCS score >= 12 (12 months)
|
33 Participants
|
37 Participants
|
70 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS).
GCS score >= 12 (90 days)
|
30 Participants
|
37 Participants
|
67 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS).
GCS score < 12 (6 months)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS).
GCS score < 12 (12 months)
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Valacyclovir
Serious events: 16 serious events
Other events: 36 other events
Deaths: 0 deaths
Placebo
Serious events: 29 serious events
Other events: 39 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Valacyclovir
n=40 participants at risk
four 500 mg tablets 3 times a day for 90 days
|
Placebo
n=47 participants at risk
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
|---|---|---|
|
Infections and infestations
Urinary tract infection
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Infections and infestations
Urosepsis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Agitated depression
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Amnesia
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Aphasia
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Asthenia
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Hepatobiliary disorders
Billiary dyskinesia
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Blood creatinine increased
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Brain abscess
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/40
|
0.00%
0/47
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/40
|
0.00%
0/47
|
|
Nervous system disorders
Cerebral infarction
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Cerebrovascular accident
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Blood and lymphatic system disorders
Coagulopathy
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/40
|
0.00%
0/47
|
|
Nervous system disorders
Convulsion
|
5.0%
2/40 • Number of events 3
|
6.4%
3/47 • Number of events 4
|
|
Psychiatric disorders
Depression
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Vascular disorders
Embolism
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Encephalitis
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Encephalitis herpes
|
2.5%
1/40 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/40
|
4.3%
2/47 • Number of events 2
|
|
Nervous system disorders
Headache
|
5.0%
2/40 • Number of events 2
|
2.1%
1/47 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Surgical and medical procedures
Lymphadenectomy
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/40
|
2.1%
1/47 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
5.0%
2/40 • Number of events 3
|
4.3%
2/47 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Metabolism and nutrition disorders
Obesity
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Olfactory nerve disorder
|
0.00%
0/40
|
2.1%
1/47 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Otitis media
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Parkinson's disease
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/40
|
4.3%
2/47 • Number of events 2
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.5%
1/40 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Eye disorders
Retinal ischaemia
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Simple partial seizures
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Suicide attempt
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Syncope
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Toxic skin eruption
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Wound infection
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
Other adverse events
| Measure |
Valacyclovir
n=40 participants at risk
four 500 mg tablets 3 times a day for 90 days
|
Placebo
n=47 participants at risk
four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Gastrointestinal disorders
Abdominal distension
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Gastrointestinal disorders
Abdominal pain
|
2.5%
1/40 • Number of events 1
|
6.4%
3/47 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Ageusia
|
5.0%
2/40 • Number of events 2
|
0.00%
0/47
|
|
Psychiatric disorders
Aggression
|
0.00%
0/40
|
2.1%
1/47 • Number of events 2
|
|
Psychiatric disorders
Agitation
|
2.5%
1/40 • Number of events 2
|
0.00%
0/47
|
|
Investigations
Alanine aminotransferase abnormal
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 2
|
|
Investigations
Alanine aminotransferase decreased
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
5.0%
2/40 • Number of events 2
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Amnesia
|
2.5%
1/40 • Number of events 2
|
0.00%
0/47
|
|
Nervous system disorders
Anosmia
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Psychiatric disorders
Anxiety
|
12.5%
5/40 • Number of events 5
|
6.4%
3/47 • Number of events 4
|
|
Nervous system disorders
Aphasia
|
0.00%
0/40
|
4.3%
2/47 • Number of events 2
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
2.5%
1/40 • Number of events 2
|
0.00%
0/47
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.0%
2/40 • Number of events 2
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Asthenia
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.0%
2/40 • Number of events 2
|
4.3%
2/47 • Number of events 2
|
|
Investigations
Blood alkaline phosphatase increased
|
2.5%
1/40 • Number of events 2
|
0.00%
0/47
|
|
Investigations
Blood creatinine abnormal
|
2.5%
1/40 • Number of events 2
|
0.00%
0/47
|
|
Investigations
Blood creatinine increased
|
7.5%
3/40 • Number of events 4
|
4.3%
2/47 • Number of events 3
|
|
Investigations
Blood glucose abnormal
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Blood glucose increased
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Blood lactate dehydrogenase
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Blood pressure increased
|
0.00%
0/40
|
4.3%
2/47 • Number of events 2
|
|
Investigations
Blood sodium decreased
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Blood urea
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Blood urea increased
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Blood uric acid abnormal
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Blood uric acid decreased
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Blood uric acid increased
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Brain abscess
|
2.5%
1/40 • Number of events 2
|
0.00%
0/47
|
|
Infections and infestations
Candidiasis
|
5.0%
2/40 • Number of events 2
|
0.00%
0/47
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Cerebral infarction
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular accident
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
General disorders
Chest pain
|
7.5%
3/40 • Number of events 3
|
6.4%
3/47 • Number of events 3
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/40
|
2.1%
1/47 • Number of events 3
|
|
Psychiatric disorders
Confusional state
|
2.5%
1/40 • Number of events 1
|
4.3%
2/47 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
10.0%
4/40 • Number of events 4
|
6.4%
3/47 • Number of events 3
|
|
Nervous system disorders
Convulsion
|
2.5%
1/40 • Number of events 1
|
12.8%
6/47 • Number of events 9
|
|
Nervous system disorders
Coordination abnormal
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Creatinine renal clearance decreased
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Infections and infestations
Cystitis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 2
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Depressed level of consciousness
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Psychiatric disorders
Depression
|
17.5%
7/40 • Number of events 8
|
12.8%
6/47 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhoea
|
2.5%
1/40 • Number of events 1
|
6.4%
3/47 • Number of events 4
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Diverticulitis
|
2.5%
1/40 • Number of events 5
|
0.00%
0/47
|
|
Nervous system disorders
Dizziness
|
5.0%
2/40 • Number of events 2
|
4.3%
2/47 • Number of events 2
|
|
Gastrointestinal disorders
Dry mouth
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Dysaesthesia
|
2.5%
1/40 • Number of events 2
|
0.00%
0/47
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Dyscalculia
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Dysesthesia extremity
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
5.0%
2/40 • Number of events 2
|
0.00%
0/47
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
4/40 • Number of events 4
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Dysphagia
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 2
|
|
Nervous system disorders
Encephalitis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Encephalitis herpes
|
5.0%
2/40 • Number of events 2
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Eosinophil count abnormal
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/40
|
4.3%
2/47 • Number of events 2
|
|
Nervous system disorders
Extensor plantar response
|
0.00%
0/40
|
2.1%
1/47 • Number of events 2
|
|
General disorders
Fatigue
|
15.0%
6/40 • Number of events 6
|
12.8%
6/47 • Number of events 7
|
|
General disorders
Feeling cold
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Infections and infestations
Fungal infection
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/40
|
4.3%
2/47 • Number of events 2
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Genital candidiasis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Genital infection
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Gingival hyperplasia
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Gastrointestinal disorders
Gingivitis
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Global anmesia
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/40
|
4.3%
2/47 • Number of events 3
|
|
Investigations
Haematocrit abnormal
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Haemoglobin abnormal
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Haemoglobin decreased
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Haemorrhage intracranial
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Psychiatric disorders
Hallucinaion
|
5.0%
2/40 • Number of events 2
|
4.3%
2/47 • Number of events 2
|
|
Nervous system disorders
Headache
|
30.0%
12/40 • Number of events 14
|
14.9%
7/47 • Number of events 10
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/40
|
6.4%
3/47 • Number of events 3
|
|
Infections and infestations
Herpes zoster
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Hyperaesthesia
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Hyperreflexia
|
5.0%
2/40 • Number of events 2
|
0.00%
0/47
|
|
Nervous system disorders
Hypertonia
|
2.5%
1/40 • Number of events 2
|
4.3%
2/47 • Number of events 2
|
|
Nervous system disorders
Hypoaesthesia
|
10.0%
4/40 • Number of events 4
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Hypomania
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Infections and infestations
Influenza
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Injection site vesicles
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
12.5%
5/40 • Number of events 5
|
12.8%
6/47 • Number of events 6
|
|
General disorders
Irritability
|
5.0%
2/40 • Number of events 2
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Leg paresis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Loss of consciousness
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Mental status change
|
0.00%
0/40
|
2.1%
1/47 • Number of events 2
|
|
Nervous system disorders
Meralgia paraesthetica
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Migraine
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.0%
2/40 • Number of events 2
|
0.00%
0/47
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/40
|
4.3%
2/47 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Nail infection
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
40.0%
16/40 • Number of events 20
|
25.5%
12/47 • Number of events 18
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Nervousness
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Neutrophil count abnormal
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Psychiatric disorders
Nightmares
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Nystagmus
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Obsessive-compulsive disorder
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
General disorders
Oedema peripheral
|
2.5%
1/40 • Number of events 1
|
4.3%
2/47 • Number of events 3
|
|
Infections and infestations
Oesophageal candidiasis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Onychomycosis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/40
|
4.3%
2/47 • Number of events 2
|
|
Gastrointestinal disorders
Oral discomfort
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Oral herpes
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Otitis externa
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Otitis media
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Pain
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/40
|
4.3%
2/47 • Number of events 3
|
|
Psychiatric disorders
Panic attack
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Paraesthesia
|
5.0%
2/40 • Number of events 2
|
0.00%
0/47
|
|
Nervous system disorders
Parkinson's Disease
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Parosmia
|
5.0%
2/40 • Number of events 2
|
0.00%
0/47
|
|
Infections and infestations
Pharyngitis
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Infections and infestations
Pharyngitis streptococcal
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Platelet count increased
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/40
|
6.4%
3/47 • Number of events 3
|
|
Investigations
Protein urine present
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Pyloric abscess
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Pyrexia
|
7.5%
3/40 • Number of events 3
|
10.6%
5/47 • Number of events 5
|
|
Nervous system disorders
Radial nerve palsy
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Red blood cell count abnormal
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Reticulocyte count abnormal
|
5.0%
2/40 • Number of events 2
|
0.00%
0/47
|
|
Infections and infestations
Rhinitis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Sensory loss
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Sialoadenitis
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Infections and infestations
Sinusitis
|
0.00%
0/40
|
4.3%
2/47 • Number of events 2
|
|
Infections and infestations
Soft tissue infection
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Somnolence
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Stress
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Swelling
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Syncope
|
7.5%
3/40 • Number of events 3
|
0.00%
0/47
|
|
Nervous system disorders
Syncope vasovagal
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Thirst
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Tooth loss
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Torticollis
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Tremor
|
7.5%
3/40 • Number of events 3
|
8.5%
4/47 • Number of events 5
|
|
Infections and infestations
Upper respiratory tract infection
|
2.5%
1/40 • Number of events 1
|
4.3%
2/47 • Number of events 3
|
|
Infections and infestations
Urinary tract infection
|
17.5%
7/40 • Number of events 11
|
10.6%
5/47 • Number of events 6
|
|
Investigations
Urine analysis abnormal
|
2.5%
1/40 • Number of events 2
|
0.00%
0/47
|
|
Investigations
Urine leukocyte esterase
|
0.00%
0/40
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Urosepsis
|
2.5%
1/40 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
4/40 • Number of events 5
|
4.3%
2/47 • Number of events 2
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
Weight decreased
|
10.0%
4/40 • Number of events 4
|
6.4%
3/47 • Number of events 4
|
|
Investigations
Weight increased
|
2.5%
1/40 • Number of events 1
|
0.00%
0/47
|
|
Investigations
White blood cells urine positive
|
5.0%
2/40 • Number of events 3
|
2.1%
1/47 • Number of events 3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place