A Double-blind, Placebo-controlled, Randomized INTerventi... | NCT03452488

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.	Drug: Placebo
175mg BIO101	Experimental	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.	Drug: BIO101
350mg BIO101	Experimental	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.	Drug: BIO101

Name	Type	Description	Arm Group Labels	Other Names
BIO101	Drug	Oral capsules	175mg BIO101 350mg BIO101

Measure	Description	Time Frame
Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test	Gait speed was measured using the 400 MW test, which measured how long it took the participant to walk a distance of 400 meters. Missing data imputed using adjusted Bayesian Multiple Imputation (MI) methods for Non-Completers who failed to perform the Test feasibility and Multiple Imputation for participants who without data on on-Site visit. Data up to 9 months was used where 6 months data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months

Measure	Description	Time Frame
Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score	The Physical Function Domain (PF-10) of the SF-36 assesses an individual's perceived physical functioning and limitations in various activities. It consists of ten items that ask about a person's ability to perform different physical activities and tasks. Scores on the PF-10 range from 0 to 100 where 100 indicates no physical limitations. Missing data imputed using adjusted Bayesian MI methods. Data up to 9 month was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Name	Affiliation	Role
Rob Van Maanen	Biophytis	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Advanced Clinical Research		Banning	California	92221	United States
SC Clinical Research, Inc

ID	Title	Description
FG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
FG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 20, 2020	Dec 14, 2023

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 to 6 Months in Gait Speed for 400 Meter Walking (MW) Test

Gait speed was measured using the 400 MW test, which measured how long it took the participant to walk a distance of 400 meters. Missing data imputed using adjusted Bayesian Multiple Imputation (MI) methods for Non-Completers who failed to perform the Test feasibility and Multiple Imputation for participants who without data on on-Site visit. Data up to 9 months was used where 6 months data were unavailable for participants enrolled during the COVID-19 pandemic.

Full Analysis Set: The Full Analysis Set (FAS) population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.

One participant randomized but not treated with 175 mg BIO101.

Posted

Least Squares Mean

95% Confidence Interval

Meter/Second (m/s)

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.
OG002	350mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.

Units	Counts
Participants	OG00079 OG00175 OG00276

Title

Denominators

Categories

Gait Speed based on Mixed Effect Model

- ParticipantsOG00032
- ParticipantsOG00134
- ParticipantsOG00240

Title	Measurements

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 OG001	Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic.	Mixed Models Analysis		0.2437														Superiority
OG000 OG002	Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic

Secondary

Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score

The Physical Function Domain (PF-10) of the SF-36 assesses an individual's perceived physical functioning and limitations in various activities. It consists of ten items that ask about a person's ability to perform different physical activities and tasks. Scores on the PF-10 range from 0 to 100 where 100 indicates no physical limitations. Missing data imputed using adjusted Bayesian MI methods. Data up to 9 month was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.
OG002	350mg BIO101

Secondary

Change From Baseline to 6 Months in Handgrip Strength Test

Handgrip strength was a commonly used measure of upper body skeletal muscle function and had been widely used as a general indicator of frailty with predictive validity for both mortality and functional limitations. Participants were instructed to stand upright and with the dynamometer beside them but not against their body. Strength was measured three times for both hands. The highest value of all 3 attempts was kept for further analysis. Grip strength was measured in the dominant hand using a hydraulic grip strength dynamometer. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

kilograms (Kg)

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.

Secondary

Change From Baseline to 6 Months in Appendicular Lean Body Mass (ALM) Based on Dual-energy X-ray Absorptiometry (DEXA) Measurements

DEXA scans provided accurate measurements of body composition, recording fat and lean mass distribution throughout the entire body. Foundation of National Health Institute (FNIH) project report recommended ALM alone was used to measure gender-specific low muscle mass. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.
OG002	350mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.

Secondary

Rate of Response for Completing 400 MW Test After 6 Months

A responder was defined as an improvement (increase) of 0.1 m/s or more in 400MW gait speed test compared to baseline. A non-responder was defined as a participant that was not a responder. Participants with a missing value at the visit and/or missing baseline value were considered as non-responders. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Count of Participants

Participants

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.
OG002	350mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.

Secondary

Change From Baseline to 6 Months in Muscle Strength Based on Knee Extension

Isometric knee extension torque was measured with a knee extension dynamometer chair. The participants were positioned in an upright position, with straps to affix the hips to the chair and the ankle to a force or torque transducer at the knee angle of 90°. Lever arm length was recorded as the distance between the knee axis of rotation and the middle of the pad. Knee extension was measured using the maximum peak torque measurement Newton meter (Nm) for 60°/s, 90°/s and 180°/s for the tested leg (either right or left). The Knee extension torque was obtained either directly or by multiplying recorded peak force with the lever arm length. The assay with the highest torque output was taken for analyses. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

Newton meter (Nm)

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101

Secondary

Change From Baseline to 6 Months in Time for Five Chair Stands as Part of the Short Physical Performance Battery (SPPB) Assessment

The SPPB was a series of tests designed to examine physical movements. The chair stands tests involved standing from a chair a number of times to test leg strength. Each performance measures were assigned a score ranging from 0 to 4, with 4 indicating the highest level of performance and 0 the inability to complete the test. The time to complete the task was recorded. The time required to perform five chair stands was scored as follows: ≥ 16.70 sec = 1; 13.70 to 16.69 sec = 2; 11.20 to 13.69 sec = 3; ≤ 11.19 = 4. A score of 0 was assigned to participants unable to perform the task. A summary score ranging from 0 (worst performers) to 12 (best performers) was calculated by adding sub scores from the chair stands test. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

Seconds

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101

Secondary

Change From Baseline to 6 Months in Distance in the 6-Minute Walk Test (6MWT)

The 6MWT was a test for functional exercise capacity and involved measuring the distance a participant could cover within the allotted time of 6 minutes. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

Meters

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.
OG002	350mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.

Secondary

Change From Baseline to 6 Months in Pepper Assessment Tool for Disability (PAT-D) for Obese Participants

The PAT-D was a disability questionnaire which asked respondents how much difficulty they had with a range of activities with functioning. PAT-D scores range from 1 (worst) to 5 (best). Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.
OG002	350mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.

Secondary

Change From Baseline to 6 Months in SPPB Total Score

The SPPB was a series of tests designed to examine physical movements. Results of the SPPB included total gait speed score, total balance test score, and total chair stand score. The first tests examined balance (without the assistance of a cane or walker) with the feet in three different orientations, the second test examined gait speed, and the third tests involved standing from a Chair a number of times to test leg strength. A score of 0 was assigned to participants unable to perform the task. A summary score ranging from 0 (worst performers) to 12 (best performers) was calculated by adding sub scores from the walking speed, chair stands and balance tests. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.

Secondary

Change From Baseline to 6 Months in Sarcopenia Quality of Life (SarQoL) Auto-Evaluation Questionnaire

The SarQoL was a sarcopenia-specific, self-administered, quality of life questionnaire designed for community-dwelling elderly study participants aged 65 years and older.

The questionnaire contained 22 questions, which took approximately 10 minutes to complete. The questionnaire covered 7 domains: physical and mental health; locomotion; body composition; functionality; activities of daily living; leisure activities; and fears. Most questions are answered on a 4 point Likert scale. The total scoring of the SarQoL questionnaire ranges from 0 (worst imaginable health) to 100 (best imaginable health). A higher score reflected a higher quality of life. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101

Secondary

Change From Baseline to 6 Months in Stair Climb Power Test (SCPT)

The SCPT measured the ability to ascend and descend stairs and tests lower body strength and balance and measures time (in seconds) taken to ascend and descend a flight of stairs (10 steps with a 20 cm step height; a handrail was recommended). Step heights should have been suitable (between 16 and 20 cm). Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

Seconds

Baseline and 6 Months

ID	Title	Description
OG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
OG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.
OG002	350mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
AV block third degree	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Chest pain	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Ischemic stroke	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Recurrent cardiac decompensation	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Unstable angina	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Calculous cholecystitis	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Partial bowel obstruction	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Small bowel obstruction	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Toothache	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Cellulitis of leg	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0012 events1 affected75 at risk EG0020 events0 affected74 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Fracture of intertrochanteric section of femur, closed	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Snake bite	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Lung adenocarcinoma stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Bladder cancer recurrent	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Urinary tract infection	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Urolithiasis	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0002 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Chronic obstructive pulmonary disease exacerbation	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Shingles	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Ankle fracture	Surgical and medical procedures	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Myocardial infarction	Surgical and medical procedures	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Clot blood	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0012 events1 affected75 at risk EG0020 events0 affected74 at risk
Ischemic stroke	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Orthostatic hypotension	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Coronavirus infection	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Brain tumor	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
General discomfort	Investigations	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Chest pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
AV block third degree	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Age indeterminate inferior myocardial infarction	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Atrial fibrillation	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Chest pain	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Chest pain - cardiac	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Coronary artery disease	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Dizziness	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Dizzy on standing	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Increased blood pressure	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Ischemic stroke	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Paroxysmal atrial fibrillation	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Recurrent cardiac decompensation	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Tachycardia	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Unstable angina	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Vasovagal symptoms	Cardiac disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Anemia	Blood and lymphatic system disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Deafness temporary	Ear and labyrinth disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Persistent postural-perceptual dizziness	Ear and labyrinth disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hyperparathyroidism	Endocrine disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hypoglycaemia	Endocrine disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Central retinal vein occlusion	Eye disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Corneal abrasion	Eye disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Temporary vision loss	Eye disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Abdominal bloating	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Acid reflux (esophageal)	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Alternation between constipation and diarrhea	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Bloated feeling	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0012 events1 affected75 at risk EG0021 events1 affected74 at risk
Calculous cholecystitis	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Constipation	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0003 events3 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Diarrhea	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0013 events3 affected75 at risk EG0022 events1 affected74 at risk
Diarrhea recurrent	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Flatulence	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Food poisoning	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Frequent bowel movements	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
GERD	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
International normalized ratio increased	Blood and lymphatic system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Prothrombin deficiency	Blood and lymphatic system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0012 events1 affected75 at risk EG0020 events0 affected74 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Gastro-intestinal disorder NOS	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Gastroenteritis	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Gastrooesophageal reflux	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Ileus of intestine	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Loose stools	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Nausea	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0013 events2 affected75 at risk EG0022 events2 affected74 at risk
Partial bowel obstruction	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Small bowel obstruction	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Stomach pain	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Tooth pain	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Toothache	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Vomited	Gastrointestinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Decreased appetite	General disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
General malaise	General disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Headache	General disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Hot flashes	General disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Mucosal sores	General disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Nausea	General disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Night sweats	General disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Post fall syndrome	General disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Tiredness	General disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0021 events1 affected74 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Choledocholithiasis	Hepatobiliary disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Gallbladder polyp	Hepatobiliary disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hemangioma of liver	Hepatobiliary disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Hepatic lesion NOS	Hepatobiliary disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Impaired liver function	Hepatobiliary disorders	MedDRA version 21.0	Systematic Assessment	EG0002 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Steatosis hepatic	Hepatobiliary disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Seasonal allergy	Immune system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Cellulitis of leg	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0012 events1 affected75 at risk EG0020 events0 affected74 at risk
Common cold	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Flu	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0012 events2 affected75 at risk EG0020 events0 affected74 at risk
Influenza	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Influenza (epidemic)	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Respiratory tract infection bacterial	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Tooth infection	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0021 events1 affected74 at risk
Upper respiratory infection	Infections and infestations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Ankle injury	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Dizziness	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Fall	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0004 events4 affected81 at risk EG0012 events2 affected75 at risk EG0023 events3 affected74 at risk
Fracture of intertrochanteric section of femur, closed	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Fractured nose	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Laceration of head	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Low back strain	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Snake bite	Injury, poisoning and procedural complications	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Coronavirus test positive	Investigations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
GGT increased	Investigations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Lipase increased	Investigations	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Triglycerides high	Investigations	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Electrolyte abnormality	Metabolism and nutrition disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hyperamylasemia	Metabolism and nutrition disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hypercalcemia	Metabolism and nutrition disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hypercholesteremia	Metabolism and nutrition disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA version 21.0	Systematic Assessment	EG0002 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hyperlipasemia	Metabolism and nutrition disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Worsening of diabetes	Metabolism and nutrition disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Adhesive capsulitis of shoulder	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0022 events2 affected74 at risk
Arthropathy NOS	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Fall	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0022 events2 affected74 at risk
Fibula fracture	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Flare up of arthritis	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Foot fracture	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Fractured toe	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Gait tripping	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Leg cramps	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0022 events1 affected74 at risk
Leg pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Muscle cramps	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Muscle soreness	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0002 events1 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Myalgia of lower extremities	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0012 events2 affected75 at risk EG0020 events0 affected74 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0021 events1 affected74 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Pain in hip	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0012 events2 affected75 at risk EG0021 events1 affected74 at risk
Pain in joint involving forearm	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Pain in leg	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Pain legs	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Painful R arm	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Pelvic bone pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0022 events1 affected74 at risk
Rib pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Rotator cuff injury	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Rotator cuff tendinitis	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Sarcopenia	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Shoulder pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Stiff neck	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Carcinoma basal cell	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Lung adenocarcinoma stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Dizziness	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Essential tremor (hereditary)	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Foot drop	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Frontal headache	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Head pain	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Headache	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0021 events1 affected74 at risk
Headache NOS	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Insomnia	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Lightheadedness	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Movements disturbance NOS	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Nerve pain	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Sciatica	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Tremor aggravated	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Vascular parkinsonism	Nervous system disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Anorexia	Psychiatric disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Anxiety depression	Psychiatric disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Despondent	Psychiatric disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Difficulty sleeping	Psychiatric disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Acute cystitis	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0002 events2 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Bilateral hydronephrosis	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Bladder cancer recurrent	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Creatine kinase increased	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Cyst of kidney	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hematuria	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0002 events2 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Urinary tract infection	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0013 events3 affected75 at risk EG0020 events0 affected74 at risk
Urolithiasis	Renal and urinary disorders	MedDRA version 21.0	Systematic Assessment	EG0002 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Enlarged prostate (benign)	Reproductive system and breast disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Acute infective bronchitis	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Bronchitis	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0022 events2 affected74 at risk
Bronchitis bacterial	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
COPD	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Chest cold	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Chronic obstructive pulmonary disease exacerbation	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Coughing	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Dysphagia	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Infective exacerbation of chronic obstructive airways disease	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Nose bleed	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Pharyngitis	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0012 events2 affected75 at risk EG0020 events0 affected74 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Shortness of breath	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Sleep apnea	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Upper respiratory infection	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Allergic rash	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Cellulitis of arm	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Contact dermatitis	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hair growth increased	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hairiness	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hidradenitis suppurativa	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Itching	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Itchy skin	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Shingles	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Skin eruption	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Toe operation	Skin and subcutaneous tissue disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0023 events1 affected74 at risk
Fall	Social circumstances	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Fatigue	Social circumstances	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Ankle fracture	Surgical and medical procedures	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Inguinal hernia repair	Surgical and medical procedures	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Myocardial infarction	Surgical and medical procedures	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Right cataract extraction	Surgical and medical procedures	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Tooth extraction	Surgical and medical procedures	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Wound	Surgical and medical procedures	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Aortic aneurysm	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Clot blood	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0012 events1 affected75 at risk EG0020 events0 affected74 at risk
Hypertension worsened	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Hypotension	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected75 at risk EG0020 events0 affected74 at risk
Hypotension orthostatic	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Ischemic stroke	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Left deep vein thrombosis	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk
Orthostatic hypotension	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected75 at risk EG0021 events1 affected74 at risk
Syncope	Vascular disorders	MedDRA version 21.0	Systematic Assessment	EG0002 events1 affected81 at risk EG0010 events0 affected75 at risk EG0020 events0 affected74 at risk

ID	Term
D009133	Muscular Atrophy
D020879	Neuromuscular Manifestations
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D001284	Atrophy
D020763	Pathological Conditions, Anatomical
D013568	Pathological Conditions, Signs and Symptoms
D012816	Signs and Symptoms
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D010335	Pathologic Processes

ID	Term
D026461	Ecdysteroids
D002783	Cholestenones
D002782	Cholestenes
D002776	Cholestanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D007301	Insect Hormones
D007447	Invertebrate Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

ID	Title	Description
BG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.
BG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.
BG002	350mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.	1	81	10	81	48	81
EG001	175mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.	0	75	10	75	45	75
EG002	350mg BIO101	BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.	1	74	4	74	38	74