Trial Outcomes & Findings for Tenoten® in the Treatment of Somatoform, Stress-related and Other Neurotic Disorders (NCT NCT03036293)

Last Updated: 2020-12-31

Results Overview

The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview. Anxiety scoring: ≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder; ≥25 - severe anxiety. Higher values represent a worse outcome

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

390 participants

Primary outcome timeframe

12 weeks

Results posted on

2020-12-31

Participant Flow

Participant milestones

Participant milestones
Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo, 2 Tablets Twice Daily (4 Tablets/Day) Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Placebo: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo, 2 Tablets 4 Times Daily (8 Tablets/Day) Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Placebo: Tablet for oral use.
Overall Study STARTED	127	67	131	65
Overall Study COMPLETED	126	64	130	64
Overall Study NOT COMPLETED	1	3	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) n=127 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo, 2 Tablets Twice Daily (4 Tablets/Day) n=67 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Placebo: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) n=131 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo, 2 Tablets 4 Times Daily (8 Tablets/Day) n=65 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Placebo: Tablet for oral use.	Total n=390 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=127 Participants	0 Participants n=67 Participants	0 Participants n=131 Participants	0 Participants n=65 Participants	0 Participants n=390 Participants
Age, Categorical Between 18 and 65 years	127 Participants n=127 Participants	67 Participants n=67 Participants	131 Participants n=131 Participants	65 Participants n=65 Participants	390 Participants n=390 Participants
Age, Categorical >=65 years	0 Participants n=127 Participants	0 Participants n=67 Participants	0 Participants n=131 Participants	0 Participants n=65 Participants	0 Participants n=390 Participants
Age, Continuous	32.7 years STANDARD_DEVIATION 7.1 • n=127 Participants	34.2 years STANDARD_DEVIATION 7.4 • n=67 Participants	32.8 years STANDARD_DEVIATION 7.6 • n=131 Participants	34.8 years STANDARD_DEVIATION 8 • n=65 Participants	33.4 years STANDARD_DEVIATION 7.5 • n=390 Participants
Sex: Female, Male Female	99 Participants n=127 Participants	50 Participants n=67 Participants	102 Participants n=131 Participants	52 Participants n=65 Participants	303 Participants n=390 Participants
Sex: Female, Male Male	28 Participants n=127 Participants	17 Participants n=67 Participants	29 Participants n=131 Participants	13 Participants n=65 Participants	87 Participants n=390 Participants
Race and Ethnicity Not Collected	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Kazakhstan	6 participants n=127 Participants	6 participants n=67 Participants	9 participants n=131 Participants	2 participants n=65 Participants	23 participants n=390 Participants
Region of Enrollment Russia	121 participants n=127 Participants	61 participants n=67 Participants	122 participants n=131 Participants	63 participants n=65 Participants	367 participants n=390 Participants
HAM-A scale baseline score	18.84 units on a scale STANDARD_DEVIATION 5.81 • n=127 Participants	17.69 units on a scale STANDARD_DEVIATION 5.1 • n=67 Participants	18.53 units on a scale STANDARD_DEVIATION 4.32 • n=131 Participants	18.2 units on a scale STANDARD_DEVIATION 6.02 • n=65 Participants	18.43 units on a scale STANDARD_DEVIATION 5.32 • n=390 Participants
EQ-5D-3L baseline score	7.44 units on a scale STANDARD_DEVIATION 1.44 • n=127 Participants	7.51 units on a scale STANDARD_DEVIATION 1.13 • n=67 Participants	7.42 units on a scale STANDARD_DEVIATION 1.05 • n=131 Participants	7.47 units on a scale STANDARD_DEVIATION 1.45 • n=65 Participants	7.45 units on a scale STANDARD_DEVIATION 1.19 • n=390 Participants
Hospital Anxiety and Depression Scale (HADS)-Anxiety	13.52 units on a scale STANDARD_DEVIATION 1.79 • n=127 Participants	13.01 units on a scale STANDARD_DEVIATION 1.6 • n=67 Participants	13.49 units on a scale STANDARD_DEVIATION 1.79 • n=131 Participants	13.46 units on a scale STANDARD_DEVIATION 1.99 • n=65 Participants	13.41 units on a scale STANDARD_DEVIATION 1.79 • n=390 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.

Outcome measures

Outcome measures
Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) n=126 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) n=130 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo-2 + Placebo-4 n=128 Participants Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)
Change From Baseline in the Mean HAM-A Score at 12 Weeks of Treatment: 1. Group 1 (Tenoten®, 4 Tablets a Day); 2. Group 3 (Tenoten®, 8 Tablets a Day). Week 0	18.81 score on a scale Standard Deviation 5.81	18.38 score on a scale Standard Deviation 4.32	17.88 score on a scale Standard Deviation 5.42
Change From Baseline in the Mean HAM-A Score at 12 Weeks of Treatment: 1. Group 1 (Tenoten®, 4 Tablets a Day); 2. Group 3 (Tenoten®, 8 Tablets a Day). Week 12	7.26 score on a scale Standard Deviation 4.63	6.40 score on a scale Standard Deviation 4.02	8.48 score on a scale Standard Deviation 5.13

SECONDARY outcome

Timeframe: 4 weeks

Outcome measures

Outcome measures
Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) n=126 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) n=130 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo-2 + Placebo-4 n=128 Participants Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)
Change From Baseline in the Mean HAM-A Score at 4 Weeks of Treatment: 1.1. Group 1 (Tenoten®, 4 Tablets a Day); 1.2. Group 3 (Tenoten®, 8 Tablets a Day). Week 0	18.81 score on a scale Standard Deviation 5.81	18.38 score on a scale Standard Deviation 4.32	17.88 score on a scale Standard Deviation 5.42
Change From Baseline in the Mean HAM-A Score at 4 Weeks of Treatment: 1.1. Group 1 (Tenoten®, 4 Tablets a Day); 1.2. Group 3 (Tenoten®, 8 Tablets a Day). Week 4	13.73 score on a scale Standard Deviation 5.35	13.31 score on a scale Standard Deviation 4.7	13.85 score on a scale Standard Deviation 5.34

SECONDARY outcome

Timeframe: 8 weeks

Population: Raw data from groгps placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.

Outcome measures

Outcome measures
Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) n=126 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) n=130 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo-2 + Placebo-4 n=128 Participants Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)
The Mean HAM-A Score at 8 Weeks of Treatment: 2.1. Group 1 (Tenoten®, 4 Tablets a Day); 2.2. Group 3 (Tenoten®, 8 Tablets a Day). Week 0	18.81 score on a scale Standard Deviation 5.81	18.38 score on a scale Standard Deviation 4.32	17.88 score on a scale Standard Deviation 5.42
The Mean HAM-A Score at 8 Weeks of Treatment: 2.1. Group 1 (Tenoten®, 4 Tablets a Day); 2.2. Group 3 (Tenoten®, 8 Tablets a Day). Week 8	10.61 score on a scale Standard Deviation 5.44	9.88 score on a scale Standard Deviation 4.93	10.81 score on a scale Standard Deviation 5.16

SECONDARY outcome

Timeframe: 4,8,12 weeks

Outcome measures

Outcome measures
Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) n=126 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) n=130 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo-2 + Placebo-4 n=128 Participants Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)
Percentage of Patients Had at Least a 50% Improvement in the HAM-A Score: 3.1. Group 1 (Tenoten® 4 Tablets a Day): After 4, 8 and 12 Weeks; 3.2. Group 3 (Tenoten® 8 Tablets a Day): After 4, 8 and 12 Weeks. Week 4	16 Participants	18 Participants	14 Participants
Percentage of Patients Had at Least a 50% Improvement in the HAM-A Score: 3.1. Group 1 (Tenoten® 4 Tablets a Day): After 4, 8 and 12 Weeks; 3.2. Group 3 (Tenoten® 8 Tablets a Day): After 4, 8 and 12 Weeks. Week 8	44 Participants	55 Participants	45 Participants
Percentage of Patients Had at Least a 50% Improvement in the HAM-A Score: 3.1. Group 1 (Tenoten® 4 Tablets a Day): After 4, 8 and 12 Weeks; 3.2. Group 3 (Tenoten® 8 Tablets a Day): After 4, 8 and 12 Weeks. Week 12	88 Participants	96 Participants	69 Participants

SECONDARY outcome

Timeframe: 4,8,12 weeks

Outcome measures

Outcome measures
Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) n=126 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) n=130 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo-2 + Placebo-4 n=128 Participants Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)
Percentage of Patients With no Anxiety (HAM-A Score <14) in: 4.1. Group 1 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks; 4.3. Group 3 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks. Week 4	58 Participants	63 Participants	66 Participants
Percentage of Patients With no Anxiety (HAM-A Score <14) in: 4.1. Group 1 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks; 4.3. Group 3 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks. Week 8	91 Participants	105 Participants	96 Participants
Percentage of Patients With no Anxiety (HAM-A Score <14) in: 4.1. Group 1 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks; 4.3. Group 3 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks. Week 12	111 Participants	125 Participants	111 Participants

SECONDARY outcome

Timeframe: 12 weeks

European Quality of Life Instrument questionnaire (EQ-5D-3L) is designed for the evaluation of the quality of life.The score ranges between 5-15. Higher values represent a worse outcome.

Outcome measures

Outcome measures
Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) n=126 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) n=130 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo-2 + Placebo-4 n=128 Participants Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)
Change From Baseline in the Total EQ-5D-3L Score at 12 Weeks of Treatment in Patients From: 5.1. Group 1 (Tenoten®, 4 Tablets a Day); 5.2. Group 3 (Tenoten®, 8 Tablets a Day). Week 0	7.44 score on a scale Standard Deviation 1.44	7.42 score on a scale Standard Deviation 1.05	7.48 score on a scale Standard Deviation 1.28
Change From Baseline in the Total EQ-5D-3L Score at 12 Weeks of Treatment in Patients From: 5.1. Group 1 (Tenoten®, 4 Tablets a Day); 5.2. Group 3 (Tenoten®, 8 Tablets a Day). Week 12	5.84 score on a scale Standard Deviation 1.05	5.71 score on a scale Standard Deviation 0.82	6.05 score on a scale Standard Deviation 1.07

SECONDARY outcome

Timeframe: 12 weeks

Clinical Global Impession (CGI) provides a brief assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. Total range 0-16. Higher values represent a worse outcome

Outcome measures

Outcome measures
Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) n=126 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) n=130 Participants Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo-2 + Placebo-4 n=128 Participants Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)
Total CGI Scores in Patients From: 6.1. Group 1 (Tenoten®, 4 Tablets a Day); 6.2. Group 3 (Tenoten®, 8 Tablets a Day).	4.53 score on a scale Standard Deviation 3.21	4.55 score on a scale Standard Deviation 2.91	5.71 score on a scale Standard Deviation 3.28

Adverse Events

Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo-2 + Placebo-4

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Mikhail Putilovskiy, MD, PhD, Clinical and Medical Department Director

Materia Medica Holding

Phone: +74952761571

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Tenoten, 2 Tablets Twice Daily (4 Tablets/Day) n=127 participants at risk Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day) n=131 participants at risk Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal. Tenoten: Tablet for oral use.	Placebo-2 + Placebo-4 n=132 participants at risk Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily) Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.
Cardiac disorders Palpitation	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Cardiac disorders Supraventricular tachyarrhythmia	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Eye disorders Photophobia	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Eye disorders Retinal vascular disorder	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Gastrointestinal disorders Constipation	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Gastrointestinal disorders Dry mouth	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Investigations Heart rate increased	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Infections and infestations Bacterial vaginosis	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Infections and infestations Chronic sinusitis	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Infections and infestations Chronic tonsillitis	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Infections and infestations Cystitis	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Infections and infestations Nasopharyngitis	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Infections and infestations Respiratory tract infection	0.79% 1/127 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	2.3% 3/131 • Number of events 3 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	3.0% 4/132 • Number of events 4 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Infections and infestations Rhinitis	0.79% 1/127 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Infections and infestations Sinusitis	0.79% 1/127 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Infections and infestations Tonsillitis	0.79% 1/127 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Injury, poisoning and procedural complications Eye contusion	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Musculoskeletal and connective tissue disorders Muscle spasms	0.79% 1/127 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Musculoskeletal and connective tissue disorders Osteochondrosis	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Psychiatric disorders Irritability	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Psychiatric disorders Panic attack	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Reproductive system and breast disorders Menstruation delayed	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.79% 1/127 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Nervous system disorders Dysgeusia	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Nervous system disorders Headache	1.6% 2/127 • Number of events 2 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	3.0% 4/132 • Number of events 4 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Nervous system disorders Occipital neuralgia	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/131 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Nervous system disorders Somnolence	1.6% 2/127 • Number of events 2 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/132 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/127 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.00% 0/131 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).	0.76% 1/132 • Number of events 1 • During the study (12 weeks). Adverse/Serious adverse events were registered in patients of the Safety population (n=390).