Tenoten® in the Treatment of Somatoform, Stress-related a... | NCT03036293

NCT03036293

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Detailed Description

Design: an international, a multicenter, double-blind, randomized, parallel group placebo-controlled trial to evaluate efficacy and safety of study treatment.

The study will enroll outpatient subjects of both genders aged 18-45 years with verified diagnoses of somatoform, stress-related and other neurotic disorders (F43, F45, F48) and signs of clinically relevant anxiety according to The Hospital Anxiety and Depression scale (HADS).

After signing the informed consent form to participate in the clinical study the subject will be interviewed (complaints, medical history, concomitant therapy) and objective examination will be performed; the subject will fill HADS scale. The severity of anxiety at screening should be ≥ 11 according to HADS. If the subject meets inclusion criteria and has no exclusion criteria he/she will be enrolled into the study. The investigator will determine the severity of anxiety using НАМ-А scale; the subject will fill EQ-5D-3L questionnaire. At Visit 1 (Day 1) the subject will be randomized into one of the treatment groups:

Group 1: Tenoten® at 2 tablets twice daily (4 tablets/day);
Group 2: Placebo at 2 tablets twice daily (4 tablets/day);
Group 3: Tenoten® at 2 tablets 4 daily (8 tablets/day).
Group 4: Placebo at 2 tablets 4 daily (8 tablets/day). The first dose should be administered at Visit 1 after the visit procedures are completed. Further administration of the study product will be made according to the dosing scheme. The subject will administer the study product and will be followed for 12 weeks during which additional three visits will be made. At Visit 2 (Week 4), Visit 3 (Week 8) and Visit 4 (Week 12) the physician will record patients' complaints and physical examination data, fill HAM-A scale, check the study and concomitant therapy, assess treatment safety and patient compliance with the study treatment. At the final Visit 4 the subject will fill EQ-5D-3L questionnaire and the investigator will fill the Clinical Global Impression Scale Efficacy Index (CGI-EI).

Subjects will be allowed to take symptomatic therapy and medications for their co-morbidities during the study, except for the medicines listed in "Prohibited therapy".

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Tenoten, 2 tablets twice daily (4 tablets/day)	Experimental	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.	Drug: Tenoten
Placebo, 2 tablets twice daily (4 tablets/day)	Placebo Comparator	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.	Drug: Placebo
Tenoten, 2 tablets 4 times daily (8 tablets/day)	Experimental	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.	Drug: Tenoten
Placebo, 2 tablets 4 times daily (8 tablets/day)	Placebo Comparator	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.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Tenoten	Drug	Tablet for oral use.	Tenoten, 2 tablets 4 times daily (8 tablets/day) Tenoten, 2 tablets twice daily (4 tablets/day)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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).	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	12 weeks

Secondary Outcomes

Measure	Description	Time Frame
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).	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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients of both sexes aged 18-45 years (inclusive).
Patients diagnosed with somatoform, stress-related, and other neurotic disorders (F43, F45, and F48), in accordance with the ICD-10 criteria.
A moderate and severe anxiety (HADS score ≥ 11) documented at screening.
Patients providing signed Informed Consent form for participation in the clinical trial.
Patients of reproductive age (of both sexes) using contraceptives and contraceptive methods during the study and for 30 days after the end of participation in the trial.

Exclusion Criteria:

Moderate and severe depression symptoms recorded at screening (HADS score ≥ 11).
Organic, including symptomatic, mental disorders (F00-09).
Mental and behavioural disorders due to psychoactive substance use (F10-19).
Schizophrenia, schizotypal and delusional disorders (F20-29).
Mood [affective] disorders(F30-39).
Phobic (F40) and other anxiety disorders (F41), obsessive-compulsive disorder (F42), dissociative [conversion] disorders (F44), depersonalization-derealization syndrome (F48.1).
Behavioral syndromes associated with physiological disturbances and physical factors (F50-59).
Disorders of adult personality and behavior (F60-69).
Intellectual disabilities (F70-79).
Inflammatory and traumatic brain injuries with permanent neurological deficit.
Prior diagnosis of a class III or IV cardiovascular disease (according to the New York Heart Association, 1964)
Malignant neoplasms/suspected malignant neoplasms.
An allergy/intolerance to any of the components of medications used in the treatment.
Malabsorption syndrome (including hereditary or acquired lactase or other disaccharidase deficiency) and galactosemia.
Any conditions that, from investigator's point of view, may affect the patient's ability to participate in the trial.
Hospitalizations or surgeries scheduled for any date during the participation in the study.
Patients who, from investigator's point of view, will fail to comply with the observation requirements of the trial or with the dosing regimen of the study drugs.
Use of drugs listed in "Prohibited therapy" within a month prior to enrollment.
Drug addiction, alcohol use in the amount over 2 units of alcohol a day.
Pregnant or breast-feeding women.
Participation in other clinical trials within 3 month prior to the enrollment in this study.
Patients are related to the research personnel of the investigative site who are directly involved in the trial, or patients who are the immediate family member of the researcher. The 'immediate family member' includes husband/wife, parents, children or brothers (or sisters), regardless of whether they are natural or adopted.
Patients working for OOO "NPF "MATERIA MEDICA HOLDING", i.e. the company's employee, temporary contract worker, or appointed official responsible for carrying out the research (or the immediate relative).

Contacts/Locations Module

Name	Affiliation	Role
Vladimir Parfenov, DrMedSci	I.M. Sechenov First Moscow State Medical University (Sechenov University)	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Kazakh National Medical University named after S.D. Asfendiyarov		Almaty		050000	Kazakhstan
South - Kazakhstan State Pharmaceutical Academy

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
34930979	Derived	Parfenov VA, Kamchatnov PR, Khasanova DR, Bogdanov EI, Lokshtanova TM, Amelin AV, Maslova NN, Pizova NV, Belskaya GN, Barantsevich ER, Duchshanova GA, Kamenova SU, Kolokolov OV, Glazunov AB. The randomized clinical trial results of the anxiety treatment in patients with somatoform dysfunction and neurotic disorders. Sci Rep. 2021 Dec 20;11(1):24282. doi: 10.1038/s41598-021-03727-5.	36104393

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Placebo, 2 Tablets Twice Daily (4 Tablets/Day)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Apr 19, 2016

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Sci Rep. 2022 Sep 14;12(1):15416

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	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.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000127 ParticipantsBG00167 ParticipantsBG002131 ParticipantsBG003

Age, Continuous

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG000127 ParticipantsBG00167 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000127 ParticipantsBG00167 ParticipantsBG002

Race and Ethnicity Not Collected

Race and Ethnicity were not collected from any participant.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG0000 ParticipantsBG0010 ParticipantsBG002

Region of Enrollment

Number

participants

Title	Denominators	Categories
Kazakhstan	ParticipantsBG000127 ParticipantsBG00167 ParticipantsBG002

HAM-A scale baseline score

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, sensory, cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative.

Anxiety scoring:

≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;

≥25 - severe anxiety.

Mean

Standard Deviation

units on a scale

Title	Denominators	Categories
	ParticipantsBG000127 ParticipantsBG001

EQ-5D-3L baseline score

EQ-5D-3L questionnaire (European Quality of Life Instrument). Raw score range 5-15. The lower the better.

Mean

Standard Deviation

units on a scale

Title	Denominators	Categories
	ParticipantsBG000127 ParticipantsBG00167 ParticipantsBG002

Hospital Anxiety and Depression Scale (HADS)-Anxiety

Hospital Anxiety and Depression Scale - Anxiety subscale. Total score 0-21. The lower the better.

Mean

Standard Deviation

units on a scale

Title	Denominators	Categories
	ParticipantsBG000127 ParticipantsBG00167 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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).

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

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.

Posted

Mean

Standard Deviation

score on a scale

12 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	Placebo-2 + Placebo-4	Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)

Units	Counts
Participants	OG000126 OG001130 OG002128

Title

Denominators

Categories

Week 0

Title	Measurements
	OG00018.81± 5.81 OG00118.38± 4.32 OG00217.88± 5.42

Week 12

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	Mean score differences (begin-end) were compared	ANCOVA	Baseline score used as covariate	0.0055		Mean Difference (Final Values)	1.56			2-Sided	98.33	0.217	2.91					Superiority
OG001 OG002	Mean score differences (begin-end) were compared

Secondary

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).

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

Posted

Mean

Standard Deviation

score on a scale

4 weeks

ID	Title	Description
OG000	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.
OG001	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)

Secondary

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).

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

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.

Posted

Mean

Standard Deviation

score on a scale

8 weeks

ID	Title	Description
OG000	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.
OG001	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)

Secondary

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.

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

Posted

Count of Participants

Participants

4,8,12 weeks

ID	Title	Description
OG000	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.
OG001	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)

Secondary

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.

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

Posted

Count of Participants

Participants

4,8,12 weeks

ID	Title	Description
OG000	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.
OG001	Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)

Secondary

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).

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.

Posted

Mean

Standard Deviation

score on a scale

12 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	Placebo-2 + Placebo-4

Secondary

Total CGI Scores in Patients From: 6.1. Group 1 (Tenoten®, 4 Tablets a Day); 6.2. Group 3 (Tenoten®, 8 Tablets a Day).

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

Posted

Mean

Standard Deviation

score on a scale

12 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	Placebo-2 + Placebo-4

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	127	127	8	127
EG001	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.	131	131	12	131
EG002	Placebo-2 + Placebo-4	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.	132	132	17	132

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Palpitation	Cardiac disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0010 events0 affected131 at risk EG0021 events1 affected132 at risk
Supraventricular tachyarrhythmia	Cardiac disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0010 events0 affected131 at risk EG0021 events1 affected132 at risk
Photophobia	Eye disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Retinal vascular disorder	Eye disorders	MedDRA	Systematic Assessment	Retinal angiopathy	EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0010 events0 affected131 at risk EG0021 events1 affected132 at risk
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0010 events0 affected131 at risk EG0021 events1 affected132 at risk
Heart rate increased	Investigations	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0021 events1 affected132 at risk
Bacterial vaginosis	Infections and infestations	MedDRA	Systematic Assessment	Vaginosis bacterial NOS	EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0021 events1 affected132 at risk
Chronic sinusitis	Infections and infestations	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Chronic tonsillitis	Infections and infestations	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Cystitis	Infections and infestations	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment		EG0001 events1 affected127 at risk EG0013 events3 affected131 at risk EG0024 events4 affected132 at risk
Rhinitis	Infections and infestations	MedDRA	Systematic Assessment		EG0001 events1 affected127 at risk EG0010 events0 affected131 at risk EG0020 events0 affected132 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment		EG0001 events1 affected127 at risk EG0010 events0 affected131 at risk EG0020 events0 affected132 at risk
Tonsillitis	Infections and infestations	MedDRA	Systematic Assessment	Acute tonsillitis	EG0001 events1 affected127 at risk EG0010 events0 affected131 at risk EG0020 events0 affected132 at risk
Eye contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	Periorbital contusion	EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	Lumbar pain	EG0000 events0 affected127 at risk EG0010 events0 affected131 at risk EG0021 events1 affected132 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	Cramps in legs (calf)	EG0001 events1 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Osteochondrosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	Osteochondrosis of spine	EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Irritability	Psychiatric disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0010 events0 affected131 at risk EG0021 events1 affected132 at risk
Panic attack	Psychiatric disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0010 events0 affected131 at risk EG0021 events1 affected132 at risk
Menstruation delayed	Reproductive system and breast disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment		EG0001 events1 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	Taste metallic	EG0000 events0 affected127 at risk EG0010 events0 affected131 at risk EG0021 events1 affected132 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	Headache NOS, temporal headache, headache unilateral, headache fullness	EG0002 events2 affected127 at risk EG0011 events1 affected131 at risk EG0024 events4 affected132 at risk
Occipital neuralgia	Nervous system disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0011 events1 affected131 at risk EG0020 events0 affected132 at risk
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	Daytime sleepiness, sleepiness	EG0002 events2 affected127 at risk EG0010 events0 affected131 at risk EG0020 events0 affected132 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment		EG0000 events0 affected127 at risk EG0010 events0 affected131 at risk EG0021 events1 affected132 at risk

ID	Term
D001008	Anxiety Disorders

ID	Term
C529609	tenoten

ParticipantsBG004390

ParticipantsBG002131

ParticipantsBG004390

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 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)