Trial Outcomes & Findings for Micronized dHACM vs. Saline in the Treatment of Osteoarthritis of the Knee (NCT NCT03485157)

NCT ID: NCT03485157

Last Updated: 2023-12-11

Results Overview

Visual Analog Scale (VAS): 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

447 participants

Primary outcome timeframe

90 days

Results posted on

2023-12-11

Participant Flow

Screening visit occurred after enrollment and could possibly be the same day as randomization/treatment.

Participant milestones

Participant milestones
Measure	Micronized dHACM Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP
Double Blind Phase STARTED	223	224
Double Blind Phase COMPLETED	208	203
Double Blind Phase NOT COMPLETED	15	21
Open Label Phase STARTED	108	109
Open Label Phase COMPLETED	104	104
Open Label Phase NOT COMPLETED	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Micronized dHACM Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP
Double Blind Phase Lost to Follow-up	4	4
Double Blind Phase Adverse Event	2	1
Double Blind Phase Withdrawal by Subject	6	9
Double Blind Phase Removal by PI	3	7
Open Label Phase Lost to Follow-up	1	2
Open Label Phase Adverse Event	0	1
Open Label Phase Withdrawal by Subject	1	2
Open Label Phase Removal by PI	2	0

Baseline Characteristics

Micronized dHACM vs. Saline in the Treatment of Osteoarthritis of the Knee

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Micronized dHACM n=223 Participants Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline n=224 Participants Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP	Total n=447 Participants Total of all reporting groups
Age, Continuous	57.89 years STANDARD_DEVIATION 10.619 • n=5 Participants	58.45 years STANDARD_DEVIATION 11.294 • n=7 Participants	58.17 years STANDARD_DEVIATION 10.954 • n=5 Participants
Sex: Female, Male Female	120 Participants n=5 Participants	140 Participants n=7 Participants	260 Participants n=5 Participants
Sex: Female, Male Male	103 Participants n=5 Participants	84 Participants n=7 Participants	187 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	211 Participants n=5 Participants	212 Participants n=7 Participants	423 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	24 Participants n=5 Participants	19 Participants n=7 Participants	43 Participants n=5 Participants
Race (NIH/OMB) White	193 Participants n=5 Participants	195 Participants n=7 Participants	388 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Height (in)	67.17 Inches STANDARD_DEVIATION 4.114 • n=5 Participants	66.72 Inches STANDARD_DEVIATION 3.748 • n=7 Participants	66.94 Inches STANDARD_DEVIATION 3.937 • n=5 Participants
Weight	187.22 lbs STANDARD_DEVIATION 39.629 • n=5 Participants	185.12 lbs STANDARD_DEVIATION 40.305 • n=7 Participants	186.17 lbs STANDARD_DEVIATION 39.938 • n=5 Participants
Body Mass Index (BMI)	29.74 kg/m^2 STANDARD_DEVIATION 4.919 • n=5 Participants	29.81 kg/m^2 STANDARD_DEVIATION 5.279 • n=7 Participants	29.77 kg/m^2 STANDARD_DEVIATION 5.097 • n=5 Participants

PRIMARY outcome

Timeframe: 90 days

Population: Population: Intent To Treat Set

Visual Analog Scale (VAS): 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain

Outcome measures

Outcome measures
Measure	Micronized dHACM n=223 Participants Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline n=224 Participants Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP
Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days Value	32.8 score on a scale Standard Deviation 26.39	34.1 score on a scale Standard Deviation 26.40
Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days Change from baseline	-35.1 score on a scale Standard Deviation 26.72	-34.2 score on a scale Standard Deviation 26.87

PRIMARY outcome

Timeframe: 90 days

Population: Population: Intent To Treat Set

Western Ontario and McMaster Universities Arthritis Index (WOMAC) evaluation of Hip and Knee Osteoarthritis. Self-administered questionnaire consisting of 24 questions divided into 3 subscales: * Pain (5 questions) * Stiffness (2 questions) * Physical Function (17 questions) The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score, with a possible total score range of 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.

Outcome measures

Outcome measures
Measure	Micronized dHACM n=223 Participants Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline n=224 Participants Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP
Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days Value	26.9 score on a scale Standard Deviation 18.43	28.8 score on a scale Standard Deviation 18.98
Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days Change from baseline	-20.6 score on a scale Standard Deviation 18.16	-19.6 score on a scale Standard Deviation 17.99

PRIMARY outcome

Timeframe: 365 days

Population: Subjects with at least 1 Treatment Emergent Adverse Event reported

Number of Participants with At Least 1 Treatment Emergent Adverse Event (TEAE) Reported

Outcome measures

Outcome measures
Measure	Micronized dHACM n=223 Participants Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline n=224 Participants Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP
Primary Safety Endpoint: Number of Participants With Adverse Events (AEs)	123 Participants	120 Participants

PRIMARY outcome

Timeframe: 365 days

Population: Subjects reporting Serious Adverse Events

Number of Participants with At Least 1 Serious Treatment Emergent Adverse Event (TEAE) Reported

Outcome measures

Outcome measures
Measure	Micronized dHACM n=223 Participants Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline n=224 Participants Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP
Primary Safety Endpoint: Number of Participants With Serious Adverse Events (SAEs)	11 Participants	12 Participants

PRIMARY outcome

Timeframe: 365 days

Population: Subjects reporting Unanticipated Treatment Emergent Adverse Events

Number of Participants with At Least 1 Unanticipated Treatment Emergent Adverse Event (TEAE) Reported

Outcome measures

Outcome measures
Measure	Micronized dHACM n=223 Participants Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline n=224 Participants Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP
Primary Safety Endpoint: Number of Participants With Unanticipated Adverse Events	16 Participants	16 Participants

SECONDARY outcome

Timeframe: 180 days

Population: Population: Intent To Treat

Visual Analog Scale (VAS) : 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain

Outcome measures

Outcome measures
Measure	Micronized dHACM n=223 Participants Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline n=224 Participants Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP
Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days Value	31.1 score on a scale Standard Deviation 26.98	32.2 score on a scale Standard Deviation 27.35
Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days Change From Baseline	-36.9 score on a scale Standard Deviation 28.51	-36.1 score on a scale Standard Deviation 27.94

SECONDARY outcome

Timeframe: 180 days

Population: Population: Intent To Treat

Outcome measures

Outcome measures
Measure	Micronized dHACM n=223 Participants Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline n=224 Participants Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP
Secondary Endpoint:Change From Baseline in WOMAC at 180 Days Value	26.0 score on a scale Standard Deviation 19.45	27.6 score on a scale Standard Deviation 19.63
Secondary Endpoint:Change From Baseline in WOMAC at 180 Days Change From Baseline	-21.6 score on a scale Standard Deviation 20.91	-20.8 score on a scale Standard Deviation 20.67

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 365 days

VAS: 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 365 days

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 365 days

VAS: 0 to 100 mm horizontal visual analog scale with a higher score indicating greater satisfaction

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 365 days

Knee Injury and Osteoarthritis Outcome Score (KOOS): 5 subscales scored on a 5 point scale where the final score is summed and transformed into a 100 point scale with a higher score representing no disability and a lower score representing extreme disability

Outcome measures

Outcome data not reported

Adverse Events

Micronized dHACM

Serious events: 11 serious events

Other events: 123 other events

Deaths: 0 deaths

Saline

Serious events: 12 serious events

Other events: 120 other events

Deaths: 0 deaths

Open-Label Micronized dHACM

Serious events: 5 serious events

Other events: 94 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

MIMEDX

Phone: (770) 651-9100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Micronized dHACM n=223 participants at risk Injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP	Saline n=224 participants at risk Injection of 0.9% Sodium Chloride Injection, USP Saline: Injection of 1 mL 0.9% Sodium Chloride, USP	Open-Label Micronized dHACM n=217 participants at risk Open-label injection of micronized dHACM Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Infections and infestations Diverticulitis	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Infections and infestations Staphylococcal infection	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Cardiac disorders Coronary artery occlusion	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumor	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Nervous system disorders Cerebrovascular accident	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Surgical and medical procedures Knee arthroplasty	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Ear and labyrinth disorders Vertigo	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Renal and urinary disorders Nephrolithiasis	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Renal and urinary disorders Renal cyst haemorrhage	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Skin and subcutaneous tissue disorders Cutaneous lupus erythematosus	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Vascular disorders Deep vein thrombosis	0.45% 1/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.89% 2/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.46% 1/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Musculoskeletal and connective tissue disorders Tenosynovitis	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Infections and infestations Cellulitis	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Cardiac disorders Cardiac failure congestive	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Nervous system disorders Syncope	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
General disorders Injection site joint pain	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Metabolism and nutrition disorders Dehydration	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Surgical and medical procedures Cardiac pacemaker replacement	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.45% 1/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Injury, poisoning and procedural complications Fall	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.46% 1/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.46% 1/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Injury, poisoning and procedural complications Overdose	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.46% 1/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/223 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.00% 0/224 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.	0.46% 1/217 • Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.