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Clinical Trial Results:
OSU6162 IN THE TREATMENT OF FATIGUE AND OTHER NEUROPSYCHOLOGICAL SEQUELAE AFTER ANEURYSMAL SUBARACHNOIDAL HEMORRHAGE - A DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED STUDY

Summary
EudraCT number	2016-004739-19
Trial protocol	NO
Global end of trial date	13 Sep 2019

Results information
Results version number	v1(current)
This version publication date	16 Nov 2021
First version publication date	16 Nov 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

OSU6162aSAH

ISRCTN number

US NCT number

NCT03209830

WHO universal trial number (UTN)

Sponsor organisation name

Oslo University Hospital

Sponsor organisation address

Sognvannsveien 20, Oslo, Norway,

Public contact

Rikshospitalet, Dept.of Neurosurger, Oslo University Hospital, 47 23074300, angelika.sorteberg@ous-hf.no

Scientific contact

Rikshospitalet, Dept.of Neurosurger, Oslo University Hospital, 47 23074300, angelika.sorteberg@ous-hf.no

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

07 May 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Sep 2019

Global end of trial reached?

Yes

Global end of trial date

13 Sep 2019

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study is to evaluate the efficacy and safety of OSU6162 with respect to sequela after aneurysmal subarachnoid haemorrhage with special emphasis on fatigue. The primary endpoint was change from baseline in Fatigue Severity Scale (FSS) after 12 weeks of treatment with (-)-OSU6162 or placebo, with data collection at weeks 1, 4, 8, 12, and 20 (20=8 weeks after treatment). The secondary endpoints include change from baseline in total score on the following questionnaires: - Beck Depression Inventory (BDI-II) - Beck Anxiety Inventory (BAI) - Mental Fatigue Scale (MFS) - Short Form 36 (SF-36) at week 4, 12, and 20 (i.e. at 8 weeks after treatment) Change in neuropsychological test performance from baseline to week 12 of treatment

Protection of trial subjects

Vital signs were checked at every visit along with ECG at every visit in order to detect any changes in QTc interval. Monthly pregnancy test in women of childbearing potential. Check of vital signs, physical and neurological examinations at every visit. Safety blood tests, and urine samples at week 8 and 12 Study participants were handed out a telephone number that was answered 24/7/365 and they were encouraged to make contact for any questions in relation to the study and to report any new symptoms, signs of discomfort, or when they needed to start a new concomitant medication

Background therapy

None

Evidence for comparator

Fatigue represents a major problem in good outcome survivors of aneurysmal subarachnoid hemorrhage. The character of this fatigue is mostly a mental fatigue. The underlying cause of central fatigue is not well understood, but imbalance of serotonin and foremost dopamine have been suggested (dopamine imbalance theory). Dopamine is a regulator of motivation and effortful behaviour and imbalance in the dopaminergic pathways has been linked to fatigue and cognitive dysfunction. The serotonergic system is important for neuroplasticity, emotional responses and sleep. (-)-OSU6162 is a monoaminergic stabilizer affecting both neurotransmitter systems. Clinical trials investigating the effect of (-)-OSU6162 on fatigue and other sequels after stroke and traumatic brain injury have shown promising results and these two disease are closely related to the patient cohort investigated in this study. (-)-OSU6162 also mitigated fatigue and improved mood and health-related quality of life in patients with chronic fatigue syndrome or multiple sclerosis. Hithertho no effective treatment of post aneurysmal hemorrhage fatigue is known.

Actual start date of recruitment

01 May 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Norway: 96

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

All patients with aneurysmal subarachnoid hemorrhage (aSAH) between January 2012 and March 2018 were identified and phoned for an interview that included assessment of the Fatigue Severity Scale (FSS). Those with mean FSS score ≥ 4 and without exclusion criteria were invited to a screening visit.

Screening details

There were 749 eligible patients with aSAH. Of these, 216 were dead and 103 did not meet the inclusion criteria. 430 had a telephone interview. Of these 156 did not meet the inclusion criteria, 30 could not be traced, 62 had medical exclusion criteria and 82 did not want to participate.

Period 1 title

Randomization period baseline (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Assessor

Are arms mutually exclusive

Yes

(-)-OSU6162

Arm description

(-)-OSU6162 came as tablets containing 15mg of 3-(3-methanesulfonyl-phenyl)-1-propyl-piperidine hydrochloride. (-)-OSU6162 is a monoaminergic stabilizer affecting the dopaminergic and serotonergic neurotransmitter systems by acting antagonistic at the D2 dopamine receptor and partially agonistic on the serotonergic 5-hydroxytryptamine 2A (5-HT2A)

Arm type

Active comparator

Investigational medicinal product name

(-)-OSU6162

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

The initial dosage was 30mg/day (15mg x 2). After at least 1 week of treatment, those with less than 1.5 points of improvement on the mean FSS or without other convincing positive effects had their dose increased to 60mg/day (30mg x 2). Given some positive effect (but not full response) at week 1, the dosage increase could be postponed to week 4 or 8. If not tolerated, 60mg/day was reduced immediately to 30mg/day. The tablets were swallowed whole with a glass of water before breakfast and before lunch (approximately at 08:00 and 13:00 hours).

placebo

Arm description

placebo. The placebo were round, white, 15mg strength tablets with identical coating as the active (-)-OSU6162 weighing 242mg. Inactive ingredients: cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

15mg x 2 that could be increased to 30mg x 2. Tablets are swallowed whole before breakfast and before lunch (approximately 08:00 and 13:00 hours) with a glass of water

Number of subjects in period 1	(-)-OSU6162	placebo
Started	49	47
Completed	47	44
Not completed	2	3
Adverse event, non-fatal	2	-
Lack of efficacy	-	2
Protocol deviation	-	1

Baseline characteristics

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Reporting group title

(-)-OSU6162

Reporting group description

Reporting group title

placebo

Reporting group description

Reporting group values	(-)-OSU6162	placebo	Total
Number of subjects	49	47	96
Age categorical
Units: Subjects
In utero			0
Preterm newborn infants (gestational age < 37 wks)			0
Newborns (0-27 days)			0
Infants and toddlers (28 days-23 months)			0
Children (2-11 years)			0
Adolescents (12-17 years)			0
Adults (18-64 years)			0
From 65-84 years			0
85 years and over			0
Age continuous
Units: years
arithmetic mean (standard deviation)	54.4 ± 9.5	56.2 ± 10.6	-
Gender categorical
Units: Subjects
Female	35	30	65
Male	14	17	31
FSS mean score
mean value of the 9 items of the Fatigue Severity Score
Units: points
arithmetic mean (standard deviation)	6.04 ± 0.66	5.91 ± 0.90	-
MFS sum score
Mental Fatigue Score
Units: points
arithmetic mean (standard deviation)	17.9 ± 4.7	18.4 ± 6.4	-
BAI
Beck Anxiety Inventory sum score
Units: points
arithmetic mean (standard deviation)	7.9 ± 6.3	9.9 ± 7.7	-
BDI-II
Beck depression Inventory II sum score
Units: points
arithmetic mean (standard deviation)	15.98 ± 8.11	17.53 ± 9.30	-
SF-36 physical function
t-score
Units: t-score
median (inter-quartile range (Q1-Q3))	43.3 (37.2 to 52.8)	43.3 (34.5 to 50.6)	-
SF-36 physical role function
Units: t-score
median (inter-quartile range (Q1-Q3))	38.6 (32.4 to 47.1)	36.5 (32.4 to 42.4)	-
SF-36 bodily pain
Units: t-score
median (inter-quartile range (Q1-Q3))	44.7 (37.4 to 53.2)	43.7 (37.8 to 53.3)	-
SF-36 general health
Units: t-score
median (inter-quartile range (Q1-Q3))	39.9 (36.5 to 44.4)	40.7 (38.3 to 45.1)	-
SF-36 Vitality
Units: t-score
median (inter-quartile range (Q1-Q3))	37.3 (30.7 to 43.0)	37.3 (27.1 to 42.6)	-
SF-36 Social function
Units: t-score
median (inter-quartile range (Q1-Q3))	40.0 (35.2 to 44.4)	36.4 (27.8 to 42.2)	-
SF-36 emotional role functioning
Units: t-score
median (inter-quartile range (Q1-Q3))	53.8 (31.2 to 54.8)	47.0 (30.0 to 54.8)	-
SF-36 Mental health
Units: t-score
median (inter-quartile range (Q1-Q3))	44.8 (34.9 to 52.2)	46.9 (34.4 to 52.2)	-
sensorimotor function
neuropsychological test domaine
Units: z-score
median (inter-quartile range (Q1-Q3))	-0.65 (-1.35 to 0)	-0.50 (-1.10 to 0)	-
Attention
Neuropsychological test domaine
Units: z-score
median (inter-quartile range (Q1-Q3))	0 (-0.65 to 0.60)	0 (-0.68 to 0.40)	-
psychomotor speed
Neuropsychological test domaine
Units: z-score
median (inter-quartile range (Q1-Q3))	0 (-0.65 to 0.65)	0 (-0.65 to 0.65)	-
Verbal learning
Neuropsychological test domaine
Units: z-score
median (inter-quartile range (Q1-Q3))	-0.80 (-1.50 to 0)	-0.50 (-1.00 to 0)	-
verbal memory
Neuropsychological test domaine
Units: z-score
median (inter-quartile range (Q1-Q3))	0 (-1.00 to 0.50)	0 (-1.00 to 0.50)	-
executive function
Neuropsychological test domaine
Units: z-score
median (inter-quartile range (Q1-Q3))	0 (-0.65 to 0.65)	0.35 (-0.65 to 0.65)	-

End points

Top of page

Reporting group title

(-)-OSU6162

Reporting group description

Reporting group title

placebo

Reporting group description

Primary: change in FSS to week 12

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End point title

change in FSS to week 12

End point description

End point type

Primary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: points
median (inter-quartile range (Q1-Q3))	-0.33 (-1.17 to 0.03)	-0.56 (-1.44 to 0)

Attachments

change in FSS mean score

Statistical analysis FSS

Comparison groups

(-)-OSU6162 v placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.428 ^[2]

Method

t-test, 2-sided

Parameter type

Cohens d

Point estimate

-0.168

Confidence interval

level

95%

sides

2-sided

lower limit

-0.581

upper limit

0.247

Variability estimate

Standard error of the mean

Dispersion value

0.225

Notes
[1] - Difference between FSS mean score at baseline and at week 12 - comaprison of (-)-OSU6162 group to placebo group
[2] - (-)-OSU6162 was not superior to placebo in changing the FSS mean score from baseline to week 12 of treatment

Alleviation of fatigue (FSS) by (-)-OSU6162

Statistical analysis description

change in FSS mean score from baseline to 12 weeks of treatment; i.e. treatment effect of (-)-OSU6162

Comparison groups

(-)-OSU6162 v placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0 ^[3]

Method

t-test, 2-sided

Parameter type

Cohens d

Point estimate

0.562

Confidence interval

level

95%

sides

2-sided

lower limit

0.251

upper limit

0.867

Variability estimate

Standard error of the mean

Dispersion value

0.181

Notes
[3] - The FSS mean score had decreased significantly fraom baseline to week 12 of treatment with (-)-OSU6162

Alleviation of fatigue (FSS) by placebo

Comparison groups

placebo v (-)-OSU6162

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

< 0 ^[5]

Method

t-test, 2-sided

Parameter type

Cohens d

Point estimate

0.756

Confidence interval

level

95%

sides

2-sided

lower limit

0.417

upper limit

1.089

Variability estimate

Standard error of the mean

Dispersion value

0.157

Notes
[4] - Here, we merely look at the treatment effect in the placebo arm
[5] - The FSS mean score was reduced significantly from baseline to 12 weeks of treatment with placebo

Secondary: change in MFS sum score to week 12

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End point title

change in MFS sum score to week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: points
arithmetic mean (standard deviation)	-2.81 ± 4.08	-4.69 ± 5.83

Attachments

change in MFS sum score

No statistical analyses for this end point

Secondary: change in BDI to week 12

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End point title

change in BDI to week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: points
arithmetic mean (standard deviation)	-2.68 ± 7.38	-6.39 ± 8.28

No statistical analyses for this end point

Secondary: change in BAI to week 12

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End point title

change in BAI to week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: points
arithmetic mean (standard deviation)	-0.96 ± 5.01	-3.66 ± 4.96

No statistical analyses for this end point

Secondary: change in SF-36 physical function

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End point title

change in SF-36 physical function

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: t-score
arithmetic mean (standard deviation)	2.21 ± 4.92	1.54 ± 5.66

Attachments

change in physical function

No statistical analyses for this end point

Secondary: change in SF-36 physical role function at week 12

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End point title

change in SF-36 physical role function at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: t-score
arithmetic mean (standard deviation)	2.99 ± 10.87	1.81 ± 9.26

Attachments

change in physical role function

No statistical analyses for this end point

Secondary: change in FS-36 bodily pain at week 12

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End point title

change in FS-36 bodily pain at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: t-score
arithmetic mean (standard deviation)	1.58 ± 9.03	4.21 ± 7.46

Attachments

change in bodily pain

No statistical analyses for this end point

Secondary: change in FS-36 bodily pain at week 12

Top of page

End point title

change in FS-36 bodily pain at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: t-score
arithmetic mean (standard deviation)	1.57 ± 9.03	4.21 ± 7.46

Attachments

change in bodily pain

No statistical analyses for this end point

Secondary: change in SF-36 general health

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End point title

change in SF-36 general health

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: t-score
arithmetic mean (standard deviation)	0.80 ± 4.05	1.37 ± 3.48

Attachments

change in general health

No statistical analyses for this end point

Secondary: change in SF-36 social function

Top of page

End point title

change in SF-36 social function

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: t-score
arithmetic mean (standard deviation)	4.27 ± 7.89	6.52 ± 9.15

Attachments

change in vitality

No statistical analyses for this end point

Secondary: change in SF-36 social function

Top of page

End point title

change in SF-36 social function

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: t-score
arithmetic mean (standard deviation)	0.64 ± 7.64	3.51 ± 7.35

Attachments

change in social function

No statistical analyses for this end point

Secondary: change in SF-36 emotional role function

Top of page

End point title

change in SF-36 emotional role function

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: t-score
arithmetic mean (standard deviation)	3.31 ± 14.69	5.92 ± 13.52

Attachments

change in emotional role

No statistical analyses for this end point

Secondary: change in SF-36 mental health

Top of page

End point title

change in SF-36 mental health

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: t-score
arithmetic mean (standard deviation)	1.88 ± 8.33	4.29 ± 10.29

Attachments

change in mental health

No statistical analyses for this end point

Secondary: change in sensorimotor function at week 12

Top of page

End point title

change in sensorimotor function at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: z-score
median (inter-quartile range (Q1-Q3))	-0.10 (-0.65 to 0.40)	0 (-0.65 to 0.40)

Attachments

change in sensorimotor function

No statistical analyses for this end point

Secondary: change in psychomotor speed at week 12

Top of page

End point title

change in psychomotor speed at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: z-score
arithmetic mean (inter-quartile range (Q1-Q3))	0 (-0.65 to 0.35)	0 (-0.35 to 0.34)

Attachments

change in psychomotor speed

No statistical analyses for this end point

Secondary: change in attention at week 12

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End point title

change in attention at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: z-score
median (inter-quartile range (Q1-Q3))	-0.10 (-0.60 to 0.30)	0 (-0.65 to 0.20)

Attachments

change in attention

No statistical analyses for this end point

Secondary: change in executive function at week 12

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End point title

change in executive function at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: z-score
median (inter-quartile range (Q1-Q3))	0 (-0.33 to 0.30)	0 (-0.35 to 0.30)

Attachments

change in executive function

No statistical analyses for this end point

Secondary: change in verbal learning at week 12

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End point title

change in verbal learning at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: z-score
median (inter-quartile range (Q1-Q3))	0 (-0.50 to 0.50)	0 (-0.50 to 0.50)

Attachments

change in verbal learning

No statistical analyses for this end point

Secondary: change in verbal memory at week 12

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End point title

change in verbal memory at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: z-score
median (inter-quartile range (Q1-Q3))	0 (-0.50 to 1.00)	0 (-0.50 to 1.00)

Attachments

change in verbal memory

No statistical analyses for this end point

Secondary: Safety endpoint QTc interval change from baseline to week 12

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End point title

Safety endpoint QTc interval change from baseline to week 12

End point description

End point type

Secondary

End point timeframe

change from baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: ms
arithmetic mean (standard deviation)	1.19 ± 16.36	1.70 ± 14.78

change in QTc interval from baseline

Statistical analysis description

Difference between treatment groups for change in QTc interval from baseline to week 12

Comparison groups

(-)-OSU6162 v placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.676 ^[6]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[6] - There was no difference in changes in QTc interval from baseline to week 12 between treatment groups

Secondary: Safety endpoint diastolic blood pressure change at week 12

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End point title

Safety endpoint diastolic blood pressure change at week 12

End point description

End point type

Secondary

End point timeframe

change from baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: mmHg
arithmetic mean (standard deviation)	-0.38 ± 7.87	-4.02 ± 8.85

change in diastolic blood pressure at week 12

Statistical analysis description

change in diastolic blood pressure from baseline to week 12 in both treatment groups

Comparison groups

(-)-OSU6162 v placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.042 ^[7]

Method

t-test, 2-sided

Parameter type

Cohens d

Point estimate

-0.436

Confidence interval

level

95%

sides

2-sided

lower limit

-0.85

upper limit

-0.018

Variability estimate

Standard error of the mean

Dispersion value

1.76

Notes
[7] - diastolic blood pressure decreased from baseline to week 12 in the placebo group

Secondary: safety endpoint change in systolic blood pressure at week 12

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End point title

safety endpoint change in systolic blood pressure at week 12

End point description

End point type

Secondary

End point timeframe

baseline to week 12 of treatment

End point values	(-)-OSU6162	placebo
Number of subjects analysed	47	44
Units: mmHg
arithmetic mean (standard deviation)	0.43 ± 13.90	-5.23 ± 12.20

change in systolic blood pressure

Comparison groups

(-)-OSU6162 v placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.042 ^[8]

Method

t-test, 2-sided

Parameter type

Cohens d

Point estimate

-0.431

Confidence interval

level

95%

sides

2-sided

lower limit

-0.846

upper limit

-0.014

Variability estimate

Standard error of the mean

Dispersion value

2.738

Notes
[8] - The systolic blood pressure decreased significantly from baseline to week 12 of treatment in the placebo group, but not in the (-)-OSU6162 group

Adverse events

Top of page

Timeframe for reporting adverse events

From randomization to follow-up (8 weeks after treatment)

Adverse event reporting additional description

Study participants were questionned systematically for AEs at each visit and at the telephone interview. In addition, patients had a phone number and instruction to call at any time a health-related event happened. All AEs were registered in the eCRF.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

(-)-OSU6162

Reporting group description

Reporting group title

placebo

Reporting group description

Serious adverse events	(-)-OSU6162	placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 49 (2.04%)	3 / 47 (6.38%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Injury, poisoning and procedural complications
Fractured wrist
Additional description: The patient stumbled and broke the wrist, needed a cast. No dizziness or any special reason that caused the stumbling and fall
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 49 (2.04%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Cerebellar embolism
Additional description: Patient admitted to the hospital due to severe vertigo. There was a cerebellar embolism from a vertebral artery atherosclerosis. Completely recovered.
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 49 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Anxiety attack
Additional description: Patient experienced an anxiety attack few days after completion of treatment with placebo. The attack lead to a few hours of hospital admission - patient was scared of the study being concluded
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 49 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Urinary tract infection bacterial
Additional description: Urinary tract infection requiring hospital admission for intravenous antibiotic treatment
subjects affected / exposed	0 / 49 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	(-)-OSU6162	placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	43 / 49 (87.76%)	38 / 47 (80.85%)
Cardiac disorders
Palpitations
subjects affected / exposed	3 / 49 (6.12%)	1 / 47 (2.13%)
occurrences all number	3	1
ECG changes, asymptomatic
subjects affected / exposed	3 / 49 (6.12%)	1 / 47 (2.13%)
occurrences all number	3	1
Nervous system disorders
Sleep disorder
subjects affected / exposed	11 / 49 (22.45%)	4 / 47 (8.51%)
occurrences all number	12	4
Fatigue, increased
subjects affected / exposed	10 / 49 (20.41%)	10 / 47 (21.28%)
occurrences all number	10	10
Headache
Additional description: New headache or aggravation of pre-existing headache
subjects affected / exposed	15 / 49 (30.61%)	11 / 47 (23.40%)
occurrences all number	17	12
Dizziness
subjects affected / exposed	14 / 49 (28.57%)	3 / 47 (6.38%)
occurrences all number	14	3
Dysaesthesia
subjects affected / exposed	6 / 49 (12.24%)	5 / 47 (10.64%)
occurrences all number	6	6
Blood and lymphatic system disorders
Blood test abnormal
subjects affected / exposed	4 / 49 (8.16%)	6 / 47 (12.77%)
occurrences all number	5	7
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	5 / 49 (10.20%)	6 / 47 (12.77%)
occurrences all number	5	6
Nausea
subjects affected / exposed	8 / 49 (16.33%)	7 / 47 (14.89%)
occurrences all number	11	8
Appetite disorder
subjects affected / exposed	7 / 49 (14.29%)	3 / 47 (6.38%)
occurrences all number	7	3
Respiratory, thoracic and mediastinal disorders
Common cold
subjects affected / exposed	10 / 49 (20.41%)	8 / 47 (17.02%)
occurrences all number	11	9
Influenza like illness
subjects affected / exposed	4 / 49 (8.16%)	2 / 47 (4.26%)
occurrences all number	4	2
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	3 / 49 (6.12%)	9 / 47 (19.15%)
occurrences all number	3	13
Renal and urinary disorders
Urge incontinence
subjects affected / exposed	5 / 49 (10.20%)	2 / 47 (4.26%)
occurrences all number	5	2
Psychiatric disorders
Depressed mood
subjects affected / exposed	4 / 49 (8.16%)	5 / 47 (10.64%)
occurrences all number	4	5
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	9 / 49 (18.37%)	8 / 47 (17.02%)
occurrences all number	9	10
Infections and infestations
Urinary tract infection bacterial
subjects affected / exposed	4 / 49 (8.16%)	2 / 47 (4.26%)
occurrences all number	4	2
Metabolism and nutrition disorders
Hot flush
subjects affected / exposed	5 / 49 (10.20%)	3 / 47 (6.38%)
occurrences all number	5	4

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Were there any global substantial amendments to the protocol? Yes

20 Oct 2017

The protocol specified that the IMP dosage could be increased after 1 week of treatment, but did not say explicitly that the dosage could be increased at a later point of time. We asked for the possibility to pospone the increase of dosage of (-)-OSU6162/placebo beyond week 1 if an increase in dosage was deemed necessary by the investigator. The amendment was approved 20.10.2017.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

none

http://www.ncbi.nlm.nih.gov/pubmed/34715650

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Clinical trials

Clinical Trial Results: OSU6162 IN THE TREATMENT OF FATIGUE AND OTHER NEUROPSYCHOLOGICAL SEQUELAE AFTER ANEURYSMAL SUBARACHNOIDAL HEMORRHAGE - A DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED STUDY

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: change in FSS to week 12

Primary: change in FSS to week 12

Secondary: change in MFS sum score to week 12

Secondary: change in MFS sum score to week 12

Secondary: change in BDI to week 12

Secondary: change in BDI to week 12

Secondary: change in BAI to week 12

Secondary: change in BAI to week 12

Secondary: change in SF-36 physical function

Secondary: change in SF-36 physical function

Secondary: change in SF-36 physical role function at week 12

Secondary: change in SF-36 physical role function at week 12

Secondary: change in FS-36 bodily pain at week 12

Secondary: change in FS-36 bodily pain at week 12

Secondary: change in FS-36 bodily pain at week 12

Secondary: change in FS-36 bodily pain at week 12

Secondary: change in SF-36 general health

Secondary: change in SF-36 general health

Secondary: change in SF-36 social function

Secondary: change in SF-36 social function

Secondary: change in SF-36 social function

Secondary: change in SF-36 social function

Secondary: change in SF-36 emotional role function

Secondary: change in SF-36 emotional role function

Secondary: change in SF-36 mental health

Secondary: change in SF-36 mental health

Secondary: change in sensorimotor function at week 12

Secondary: change in sensorimotor function at week 12

Secondary: change in psychomotor speed at week 12

Secondary: change in psychomotor speed at week 12

Secondary: change in attention at week 12

Secondary: change in attention at week 12

Secondary: change in executive function at week 12

Secondary: change in executive function at week 12

Secondary: change in verbal learning at week 12

Secondary: change in verbal learning at week 12

Secondary: change in verbal memory at week 12

Secondary: change in verbal memory at week 12

Secondary: Safety endpoint QTc interval change from baseline to week 12

Secondary: Safety endpoint QTc interval change from baseline to week 12

Secondary: Safety endpoint diastolic blood pressure change at week 12

Secondary: Safety endpoint diastolic blood pressure change at week 12

Secondary: safety endpoint change in systolic blood pressure at week 12

Secondary: safety endpoint change in systolic blood pressure at week 12

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
OSU6162 IN THE TREATMENT OF FATIGUE AND OTHER NEUROPSYCHOLOGICAL SEQUELAE AFTER ANEURYSMAL SUBARACHNOIDAL HEMORRHAGE - A DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED STUDY