Trial Outcomes & Findings for Explorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects (NCT NCT01703832)

NCT ID: NCT01703832

Last Updated: 2015-02-11

Results Overview

Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 65 participants
• Primary outcome timeframe: -210 minutes to +100 minutes
• Results posted on: 2015-02-11

Participant Flow

Recruitment was carried out in 2 outpatient clinics in Germany (Marburg and Essen).

All 65 healthy participants were enrolled and none were excluded prior to randomization.

Participant milestones

Measure	Neurexan® At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Overall Study STARTED	33	32
Overall Study COMPLETED	32	32
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Neurexan® At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Explorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects

Baseline characteristics by cohort

Measure	Neurexan® n=33 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.	Total n=65 Participants Total of all reporting groups
Age, Continuous	42.6 years STANDARD_DEVIATION 8.4 • n=5 Participants	41.3 years STANDARD_DEVIATION 8.3 • n=7 Participants	41.9 years STANDARD_DEVIATION 8.3 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	33 Participants n=5 Participants	32 Participants n=7 Participants	65 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	17 Participants n=7 Participants	34 Participants n=5 Participants
Region of Enrollment Germany	33 participants n=5 Participants	32 participants n=7 Participants	65 participants n=5 Participants

PRIMARY outcome

Timeframe: -210 minutes to +100 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.

Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.

Outcome measures

Measure	Neurexan® n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Acute Stress Measured by Tension	3089.4 mm*min Interval 40.0 to 20940.0	3253.4 mm*min Interval 308.0 to 19305.0

PRIMARY outcome

Timeframe: -210 minutes to +100 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.

Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.

Outcome measures

Measure	Neurexan® n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Acute Stress Measured by Nervousness	2377.3 mm*min Interval 12.0 to 9071.0	3426.8 mm*min Interval 329.0 to 14898.0

SECONDARY outcome

Timeframe: -60 minute, +15 minute , + 45 minute, +100 minute

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for efficacy. Note: -60 minute time-point had 31 evaluable Neurexan participants.

The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.

Outcome measures

Measure	Neurexan® n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Changes in Saliva Alpha Amylase +45 min	171.3 IU/mL Interval 21.0 to 786.5	138.6 IU/mL Interval 9.6 to 812.8
Changes in Saliva Alpha Amylase -60 min	155.6 IU/mL Interval 21.6 to 594.9	133.2 IU/mL Interval 11.5 to 591.8
Changes in Saliva Alpha Amylase +15 min	242.8 IU/mL Interval 28.2 to 620.3	204.9 IU/mL Interval 9.8 to 819.9
Changes in Saliva Alpha Amylase +100 min	195.8 IU/mL Interval 17.4 to 597.4	144.0 IU/mL Interval 8.0 to 509.3

SECONDARY outcome

Timeframe: -60 minutes, +15 minutes, +45 minutes, +100 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.

The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.

Outcome measures

Measure	Neurexan® n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Changes in Saliva Cortisol -60 min	7.9 nmol/mL Interval 1.6 to 27.6	8.1 nmol/mL Interval 2.8 to 8.1
Changes in Saliva Cortisol +15 min	20.3 nmol/mL Interval 2.5 to 121.1	19.8 nmol/mL Interval 3.4 to 112.9
Changes in Saliva Cortisol +45 min	18.8 nmol/mL Interval 1.2 to 65.4	20.6 nmol/mL Interval 3.4 to 89.6
Changes in Saliva Cortisol +100 min	8.6 nmol/mL Interval 1.8 to 24.9	9.4 nmol/mL Interval 2.6 to 33.6

SECONDARY outcome

Timeframe: -60 minutes, +15 minutes, +45 minutes, +100 minutes

Population: 33 participants were randomized to Neurexan and 32 to Natural Course and all randomized participants were included in the Safety Set. For plasma ACTH evaluation 31 Neurexan and 24 Natural Course participants were evaluated due to insufficient samples and the -60 min time-point had 30 evaluable Neurexan participants.

The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.

Outcome measures

Measure	Neurexan® n=31 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=24 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Changes in Plasma Adrenocorticotropic Hormone (ACTH) -60 min	20.8 ng/L Interval 6.1 to 283.8	20.0 ng/L Interval 8.0 to 113.0
Changes in Plasma Adrenocorticotropic Hormone (ACTH) +15 min	35.4 ng/L Interval 13.4 to 116.9	31.0 ng/L Interval 11.4 to 158.1
Changes in Plasma Adrenocorticotropic Hormone (ACTH) +45 min	20.4 ng/L Interval 9.1 to 55.7	20.6 ng/L Interval 7.5 to 84.1
Changes in Plasma Adrenocorticotropic Hormone (ACTH) +100 min	11.8 ng/L Interval 7.0 to 33.0	13.7 ng/L Interval 3.3 to 32.6

SECONDARY outcome

Timeframe: -60 minutes, +15 minutes, +45 minutes, +100 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. For the plasma Cortisol evaluation 31 Neurexan and 24 Natural Course participants were evaluated due to insufficient sample.

The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.

Outcome measures

Measure	Neurexan® n=31 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=24 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Changes in Plasma Cortisol -60 min	365.9 nmol/L Interval 105.1 to 918.0	337.6 nmol/L Interval 125.5 to 836.5
Changes in Plasma Cortisol +15 min	554.3 nmol/L Interval 72.2 to 971.2	544.3 nmol/L Interval 124.5 to 942.5
Changes in Plasma Cortisol +45 min	466.8 nmol/L Interval 73.7 to 842.2	506.8 nmol/L Interval 121.6 to 815.2
Changes in Plasma Cortisol +100 min	285.1 nmol/L Interval 84.0 to 735.4	251.4 nmol/L Interval 136.7 to 637.7

SECONDARY outcome

Timeframe: -60 minutes, +15 minutes, +45 minutes, +100 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. For plasma Epinephrine evaluation 30 Neurexan and 23 Natural Course participants were evaluated due to insufficient sample.

The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.

Outcome measures

Measure	Neurexan® n=30 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=23 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Changes in Plasma Catecholamines (Epinephrine) -60 min	44.6 ng/L Interval 10.0 to 108.0	37.0 ng/L Interval 11.0 to 98.6
Changes in Plasma Catecholamines (Epinephrine) +15 min	58.2 ng/L Interval 10.0 to 146.0	40.2 ng/L Interval 10.0 to 88.4
Changes in Plasma Catecholamines (Epinephrine) +45 min	37.3 ng/L Interval 10.0 to 105.0	32.0 ng/L Interval 9.1 to 95.5
Changes in Plasma Catecholamines (Epinephrine) +100 min	29.8 ng/L Interval 0.0 to 87.7	33.0 ng/L Interval 10.0 to 104.0

SECONDARY outcome

Timeframe: -60 minutes, +15 minutes, +45 minutes, +100 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. For plasma Norepinephrine evaluation 30 Neurexan and 23 Natural Course participants were evaluated due to insufficient sample.

The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.

Outcome measures

Measure	Neurexan® n=30 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=23 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Changes in Plasma Catecholamines (Norepinephrine) -60 min	484.5 ng/L Interval 249.0 to 923.0	457.0 ng/L Interval 195.0 to 797.0
Changes in Plasma Catecholamines (Norepinephrine) +15 min	575.5 ng/L Interval 299.0 to 1128.0	529.0 ng/L Interval 279.0 to 1688.0
Changes in Plasma Catecholamines (Norepinephrine) +45 min	458.0 ng/L Interval 220.0 to 889.0	459.0 ng/L Interval 223.0 to 858.0
Changes in Plasma Catecholamines (Norepinephrine) +100 min	467.0 ng/L Interval 269.0 to 938.0	372.0 ng/L Interval 189.0 to 839.0

SECONDARY outcome

Timeframe: -60 minutes, +15 minutes, +45 minutes, +100 minutes

Population: The test was only conducted in the Essen site where 15 participants randomized to Neurexan and 12 participants randomized to Natural Course could be evaluated for NK cells

The Natural Killer Cells as immune cells and stress biomarkers were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.

Outcome measures

Measure	Neurexan® n=15 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=12 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Changes in Natural Killer (NK) Cells (Subgroup) -60 min	11.8 percentage of lymphocytes Interval 5.8 to 22.6	11.2 percentage of lymphocytes Interval 5.6 to 16.5
Changes in Natural Killer (NK) Cells (Subgroup) +15 min	21.3 percentage of lymphocytes Interval 9.8 to 28.1	17.7 percentage of lymphocytes Interval 10.1 to 26.2
Changes in Natural Killer (NK) Cells (Subgroup) +45 min	11.6 percentage of lymphocytes Interval 4.6 to 14.8	8.6 percentage of lymphocytes Interval 4.3 to 12.7
Changes in Natural Killer (NK) Cells (Subgroup) +100 min	11.1 percentage of lymphocytes Interval 6.1 to 18.2	7.8 percentage of lymphocytes Interval 4.0 to 20.3

SECONDARY outcome

Timeframe: -15 minutes, 0 minutes, +15 minutes, +45 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.

Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.

The measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.

Outcome measures

Measure	Neurexan® n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Changes in Blood Pressure Systolic blood pressure -15 min	120.5 mmHg Interval 86.0 to 175.0	123.5 mmHg Interval 95.0 to 147.0
Changes in Blood Pressure Systolic blood pressure 0 min	131.0 mmHg Interval 98.0 to 204.0	136.5 mmHg Interval 96.0 to 171.0
Changes in Blood Pressure Systolic blood pressure +15 min	123.0 mmHg Interval 92.0 to 161.0	128.5 mmHg Interval 86.0 to 165.0
Changes in Blood Pressure Systolic blood pressure +45 min	121.0 mmHg Interval 77.0 to 180.0	122.0 mmHg Interval 91.0 to 160.0
Changes in Blood Pressure Diastolic blood pressure -15 min	78.0 mmHg Interval 51.0 to 120.0	79.0 mmHg Interval 56.0 to 103.0
Changes in Blood Pressure Diastolic blood pressure 0 min	83.5 mmHg Interval 59.0 to 138.0	88.5 mmHg Interval 60.0 to 114.0
Changes in Blood Pressure Diastolic blood pressure +15 min	81.5 mmHg Interval 54.0 to 115.0	83.0 mmHg Interval 54.0 to 109.0
Changes in Blood Pressure Diastolic blood pressure +45 min	78.5 mmHg Interval 40.0 to 124.0	81.0 mmHg Interval 41.0 to 109.0

SECONDARY outcome

Timeframe: -15 minutes, 0 minutes, +15 minutes, +45 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.

Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.

The measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.

Outcome measures

Measure	Neurexan® n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Changes in Heart Rate -15 min	67.0 beats per minute Interval 55.0 to 96.0	69.0 beats per minute Interval 49.0 to 98.0
Changes in Heart Rate 0 min	87.0 beats per minute Interval 67.0 to 135.0	83.0 beats per minute Interval 56.0 to 125.0
Changes in Heart Rate +15 min	68.0 beats per minute Interval 54.0 to 90.0	71.0 beats per minute Interval 44.0 to 93.0
Changes in Heart Rate +45 min	68.0 beats per minute Interval 56.0 to 96.0	72.0 beats per minute Interval 48.0 to 92.0

SECONDARY outcome

Timeframe: -90 minutes, +15 minutes, +100 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.

State anxiety and stress perception were measured by State-Trait Anxiety Inventory X1 before and after a stress test. The measurements took place 90 minutes before stress test and were repeated 15 and 100 minutes after the end of the stress test. The German version of the State-Trait-Anxiety Inventory was used and differentiates between temporary/emotional state anxiety versus personality trait anxiety. The two scales with 20 items each assess (1) anxiety as a trait (STAI-X2) and (2) anxiety as a state (STAI-XI). Answers are given in a 4-point rating scale ranging from 1 ="not at all" to 4 ="very true". For analysis of each, STAI-scale single scores were summed up to one total score, representing the state and trait anxiety. Score range is 20-80 and higher scores indicate a higher anxiety.

Outcome measures

Measure	Neurexan® n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
State Anxiety and Stress Perception Measured by STAI-X1 -90 min	32.0 units on a scale Interval 21.0 to 49.0	33.0 units on a scale Interval 22.0 to 43.0
State Anxiety and Stress Perception Measured by STAI-X1 + 15 min	51.0 units on a scale Interval 33.0 to 73.0	56.0 units on a scale Interval 29.0 to 78.0
State Anxiety and Stress Perception Measured by STAI-X1 +100 min	32.0 units on a scale Interval 21.0 to 43.0	32.0 units on a scale Interval 20.0 to 52.0

SECONDARY outcome

Timeframe: -210 minutes, +100 minutes

Population: 33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.

The SCL90 has 90 items with dimensions like depression, somatization, obsessive-compulsive disorder, social insecurity, anxiety, phobic anxiety, aggression/hostility, paranoid ideation, psychoticism and each item in a subscale ranged from 0 to 4. The lower range values are favorable outcomes and higher are worse outcomes. The modified somatic SCL90 uses the SCL90 somatization items, but instead of a 7 day timeframe asks for "now". The corresponding items from SCL90 were: 1, 4, 12, 27, 40, 42, 48, 49, 52, 53, 56, 58 and the introductory question: "How much do you currently suffer from" ("Wie sehr leiden Sie momentan unter:"). The median of the average Modified Somatic SCL90 score is reported. The average score was calculated at each time point as the sum score divided by the number of non-missing individual question results for subjects with no more than 2 missing responses. The lower values in the range represent favorable outcomes while the higher values represent worse outcomes.

Outcome measures

Measure	Neurexan® n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 Participants At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Psychological Questionnaire (Modified Somatic SCL90) -210 min	0.042 units on a scale Interval 0.0 to 0.67	0.083 units on a scale Interval 0.0 to 1.08
Psychological Questionnaire (Modified Somatic SCL90) + 100 min	0.000 units on a scale Interval 0.0 to 0.5	0.000 units on a scale Interval 0.0 to 0.33

Adverse Events

Neurexan®

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

No Intervention

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Neurexan® n=33 participants at risk At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.	No Intervention n=32 participants at risk At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.
Injury, poisoning and procedural complications Procedural Pain	3.0% 1/33 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported	3.1% 1/32 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported
Injury, poisoning and procedural complications Procedural dizziness	0.00% 0/33 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported	3.1% 1/32 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported
Injury, poisoning and procedural complications Procedural nausea	0.00% 0/33 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported	3.1% 1/32 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported
Investigations Aspartate aminotransferase increased	0.00% 0/33 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported	3.1% 1/32 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported
Investigations Alanine aminotransferase increased	0.00% 0/33 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported	3.1% 1/32 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported
Nervous system disorders Dizziness	3.0% 1/33 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported	0.00% 0/32 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported
Nervous system disorders Headache	3.0% 1/33 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported	0.00% 0/32 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported
Gastrointestinal disorders Dry Mouth	3.0% 1/33 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported	0.00% 0/32 • Randomization until individual study end All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported

Additional Information

Christine Frank, PhD

Biologische Heilmittel Heel GmbH

Phone: +49 7221 501 3188

Email: christine.frank@heel.com

Results disclosure agreements

• Principal investigator is a sponsor employee Investigator agreements in place restricting the PI from independently publishing the study results. Currently working with both PIs on several publications of the NEUPRO studies.
• Publication restrictions are in place

Restriction type: OTHER