Safety and Efficacy of Cerezyme® Infusions Every 4 Weeks Versus Every 2 Weeks in Type 1 Gaucher Disease

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00364858
• Collaborator: (none)
• Enrollment: 95
• Locations: 26
• Arms: 2
• Duration (Months): 62
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multicenter, randomized trial to compare the safety and efficacy of two dosing frequencies of Cerezyme® in patients with Gaucher disease who are currently being treated with Cerezyme®.

Approximately 90 patients will be randomized in a 2:1 (q4 : q2) ratio to one of two treatment arms at up to 26 study centers worldwide. Patients will continue to receive the same total 4-week dose that they were receiving prior to study enrollment, however, they will be randomized to receive either their total 4-week dose in two infusions, one infusion every 2 weeks or their total 4-week dose in one infusion every 4 weeks. The randomization scheme will ensure a 2:1 balance between the every 4-week versus every 2-week infusion groups, respectively.

Condition or Disease	Intervention/Treatment	Phase
Gaucher Disease, Type 1; Cerebroside Lipidosis Syndrome; Glucocerebrosidase Deficiency Disease; Glucosylceramide Beta-Glucosidase Deficiency Disease; Gaucher Disease, Non-Neuronopathic Form	Drug: Cerezyme	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IV, Multicenter, Randomized, Dose Frequency Study of the Safety and Efficacy of Cerezyme® Infusions Every Four Weeks Versus Every Two Weeks in the Maintenance Therapy of Patients With Type 1 Gaucher Disease
• Study Start Date: Dec 1, 2001
• Actual Study Completion Date: Feb 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Other: Q2 Cerezyme Patients receiving Cerezyme one infusion every 2 weeks (Q2).	Drug: Cerezyme; Cerezyme doses of 20-60U/kg every 2 weeks (Q2 Arm) or 40-120 U/kg every 4 weeks (Q4 Arm).
Other: Q4 Cerezyme Patients receiving Cerezyme one infusion every 4 weeks (Q4).	Drug: Cerezyme; Cerezyme doses of 20-60U/kg every 2 weeks (Q2 Arm) or 40-120 U/kg every 4 weeks (Q4 Arm).

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinical Success at Month 24/Discontinuation [Month 24 (or at time of discontinuation)]

   Patients are considered to be a clinical success if ALL of the following are met: The patient's hemoglobin does not fall more than 1.25g/dL for women or 1.5 g/dL for men below the patient's baseline value, platelet count does not fall more than 25% below the patient's baseline value or does not fall below 80,000 mm3, liver and spleen volumes are not greater than 20% above the patient's baseline value, no evidence of bone disease progression, including no incidence of pathologic fractures, medullary infarctions, lytic lesions or avascular necrosis and has had no bone crises during the study.

Secondary Outcome Measures

1. Mean Composite Scores of the SF-36 Health Survey at Baseline [Baseline]

   The mean composite scores (0 being worst and 100 being best) for both treatment groups at Baseline. Composite scores for both treatment groups approximated those of the general population at baseline and at Month 24.

2. Mean Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation. [Month 24 (or at time of discontinuation)]

   The mean composite scores (0 being worst and 100 being best) for both treatment groups at Month 24/Discontinuation. The mean composite scores for both treatment groups approximated those of the general population at baseline and at Month 24.

3. Mean Change From Baseline in Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation [Baseline and Month 24 (or at time of discontinuation)]

   The mean composite scores (0 being worst and 100 being best) for both treatment groups approximated those of the general population at baseline. Composite score - The overall composite scores were comprised of a standardized physical and mental component score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient must provide written informed consent prior to undergoing any study-related procedures.

• The patient has a confirmed diagnosis of Gaucher disease with a documented deficiency of glucocerebrosidase by enzyme assay

• The patient has been genotyped or will have genotyping performed within 3 months of study enrollment.

• The patient has been treated with Cerezyme for at least 2 years prior to study enrollment.

• The patient has been on a stable dose of between 20-60 U/kg every 2 weeks for at least 6 months prior to study enrollment.

• The patient is at least 18 years old.

• The patient has a hemoglobin value of ≥ 11.0 g/dL for women and ≥ 12.0 g/dL for men and a platelet count of ≥ 100,000 mm^3.

• The patient's liver volume is ≤ 1.8 x normal confirmed by MRI or CT within 6 months of randomization.

• The patient's spleen volume is ≤ 10 x normal confirmed by MRI or CT within 6 months of randomization.

• The patient has a serum creatinine < 2.0 mg/dL, an ASTand ALT < 2 x upper limit of normal and a total bilirubin < 2.0 x upper limit of normal.

• Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to randomization into the study.

Exclusion Criteria:

• The patient is pregnant.

• The patient has evidence of neurologic or pulmonary involvement with Gaucher disease confirmed by medical history.

• The patient has evidence of current or prior bleeding varices or liver infarction requiring hospitalization confirmed by medical history.

• The patient has evidence of pathologic bone fractures, medullary infarctions, lytic lesions or avascular necrosis secondary to Gaucher disease confirmed by skeletal evaluation within 6 months of randomization.

• The patient has had a bone crisis (defined as pain with acute onset which requires immobilization of the affected area, narcotics for relief of pain and may be accompanied by periosteal elevation, increased white cell count, fever or debilitation of > 3 days) within 12 months of randomization.

• Patient has received an investigational drug within 30 days of the start of their participation in this trial. Patients may not receive any other investigational product throughout the course of the study.

• The patient has a clinically significant disease (with the exception of symptoms relating to Gaucher disease), including clinically significant cardiovascular, hepatic, immunologic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in the trial or potentially decrease survival

• Patient has a medical, emotional, behavioral or psychological condition that in the judgment of the Investigator would interfere with the patient's compliance with the requirements of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Medical Center	Washington	District of Columbia	United States	20010
2	University Research Foundation for Lysosomal Storage Disease, Inc.	Coral Springs	Florida	United States	33065
3	Emory University	Atlanta	Georgia	United States	30322
4	Children's Memorial Hospital	Chicago	Illinois	United States	60614
5	Midwest Cancer Research Group, Inc.	Skokie	Illinois	United States	60076
6	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
7	Institute for Genetics Medicine Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08903
8	Holy Name Hospital	Teaneck	New Jersey	United States	07666
9	Hemophilia Center of Western New York	Buffalo	New York	United States	14215
10	New York Oncology/Hematology PC	Latham	New York	United States	12110
11	New York University	New York	New York	United States	10016
12	Mt. Sinai Medical Center	New York	New York	United States	10029
13	Duke University Medical Center	Durham	North Carolina	United States	27710
14	Children's Hospital Research Foundation	Cincinnati	Ohio	United States	45229
15	Oregon Health & Science University	Portland	Oregon	United States	97239
16	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
17	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15261
18	University of Utah	Salt Lake City	Utah	United States	84132
19	Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO)	Rio de Janeiro		Brazil	20211
20	Mount Sinai Hospital	Toronto	Ontario	Canada	ON M5G 1X5
21	Istituto Giannina Gaslini	Genova		Italy
22	Universita degli Studi di Napoli "Federico II"	Naples		Italy	80131
23	Istituto per l'Infanzia Burlo-Garofolo	Trieste		Italy	34137
24	Instytut Pomnik Centrum Zdrowia Dzeicka	Warsaw		Poland	04-736
25	Hospital Vall d´Hebrón	Barcelona		Spain	08035
26	Royal Free Hospital	London		United Kingdom	NW3 2QG

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Edward Kaye, M.D., Genzyme, a Sanofi Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00364858
• Other Study ID Numbers: CZ-011-01
• First Posted: Aug 16, 2006
• Last Update Posted: Apr 3, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by , ,: Type 1 Gaucher Disease; Glucocerebrosidase Deficiency Disease
• Additional relevant MeSH terms: Gaucher Disease; Lipidoses; Deficiency Diseases

Study Results

Participant Flow

Recruitment Details	Eligible patients were randomized 2:1 to receive Cerezyme either once every 4 weeks (Q4) or once every 2 weeks (Q2) for 24 months. The studied period was from 14 December 2001 through 01 February 2007. There were 26 centers worldwide (18 United States, 1 Canada, 6 Europe, and 1 Brazil); 25 centers randomized patients to treatment.

Arm/Group Title	Q2 Cerezyme	Q4 Cerezyme
Arm/Group Description	Patients receiving Cerezyme one infusion every 2 weeks (Q2).	Patients receiving Cerezyme one infusion every 4 weeks(Q4).
Period Title: Overall Study
STARTED	33	62
COMPLETED	26	40
NOT COMPLETED	7	22

Baseline Characteristics

Arm/Group Title	Q2 Cerezyme	Q4 Cerezyme	Total
Arm/Group Description	Patients receiving Cerezyme one infusion every 2 weeks (Q2).	Patients receiving Cerezyme one infusion every 4 weeks(Q4).	Total of all reporting groups
Overall Participants	33	62	95
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.8 (17.40)	47.8 (14.47)	46.8 (15.53)
Sex: Female, Male (Count of Participants)
Female	13 39.4%	34 54.8%	47 49.5%
Male	20 60.6%	28 45.2%	48 50.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinical Success at Month 24/Discontinuation
Description	Patients are considered to be a clinical success if ALL of the following are met: The patient's hemoglobin does not fall more than 1.25g/dL for women or 1.5 g/dL for men below the patient's baseline value, platelet count does not fall more than 25% below the patient's baseline value or does not fall below 80,000 mm3, liver and spleen volumes are not greater than 20% above the patient's baseline value, no evidence of bone disease progression, including no incidence of pathologic fractures, medullary infarctions, lytic lesions or avascular necrosis and has had no bone crises during the study.
Time Frame	Month 24 (or at time of discontinuation)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population. All patients who enrolled in the study and received AT LEAST ONE infusion were included in the ITT population.

Arm/Group Title	Q2 Cerezyme	Q4 Cerezyme
Arm/Group Description	Patients receiving Cerezyme one infusion every 2 weeks (Q2).	Patients receiving Cerezyme one infusion every 4 weeks(Q4).
Measure Participants	26	57
Number of participants with Clinical Success	21	36
Proportion of participants with Clinical Success	0.808	0.632

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Q2 Cerezyme, Q4 Cerezyme
	Comments	Difference in proportion of Clinical Success = (Proportion of participants with Clinical Success Q4 - Proportion of participants with Clinical Success Q2).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Agresti and Min
	Estimated Value	-0.176
	Confidence Interval	() 95%; -0.357 to 0.058
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Composite Scores of the SF-36 Health Survey at Baseline
Description	The mean composite scores (0 being worst and 100 being best) for both treatment groups at Baseline. Composite scores for both treatment groups approximated those of the general population at baseline and at Month 24.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Quality of life was evaluated and measured by the SF-36 questionnaire.

Arm/Group Title	Q2 Cerezyme	Q4 Cerezyme
Arm/Group Description	Patients receiving Cerezyme one infusion every 2 weeks (Q2).	Patients receiving Cerezyme one infusion every 4 weeks(Q4).
Measure Participants	33	61
Composite Physical Health	49.8 (8.41)	46.9 (10.26)
Composite Mental Health	52.9 (7.6)	53.0 (8.47)

3. Secondary Outcome

Title	Mean Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation.
Description	The mean composite scores (0 being worst and 100 being best) for both treatment groups at Month 24/Discontinuation. The mean composite scores for both treatment groups approximated those of the general population at baseline and at Month 24.
Time Frame	Month 24 (or at time of discontinuation)

Outcome Measure Data

Analysis Population Description

Quality of life was evaluated and measured by the SF-36 questionnaire.

Arm/Group Title	Q2 Cerezyme	Q4 Cerezyme
Arm/Group Description	Patients receiving Cerezyme one infusion every 2 weeks (Q2).	Patients receiving Cerezyme one infusion every 4 weeks(Q4).
Measure Participants	25	53
Composite Physical Health	49.1 (7.52)	46.2 (12.39)
Composite Mental Health	53.8 (8.47)	52.6 (7.35)

4. Secondary Outcome

Title	Mean Change From Baseline in Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation
Description	The mean composite scores (0 being worst and 100 being best) for both treatment groups approximated those of the general population at baseline. Composite score - The overall composite scores were comprised of a standardized physical and mental component score.
Time Frame	Baseline and Month 24 (or at time of discontinuation)

Outcome Measure Data

Analysis Population Description

Quality of life was evaluated and measured by the SF-36 questionnaire.

Arm/Group Title	Q2 Cerezyme	Q4 Cerezyme
Arm/Group Description	Patients receiving Cerezyme one infusion every 2 weeks (Q2).	Patients receiving Cerezyme one infusion every 4 weeks(Q4).
Measure Participants	25	52
Composite Physical Health	-1.5 (7.40)	-0.5 (7.33)
Composite Mental Health	0.6 (6.48)	-0.5 (7.34)

Adverse Events

Adverse Event Reporting Description	In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.
Arm/Group Title	Q2 Cerezyme		Q4 Cerezyme		Total
Arm/Group Description	Patients receiving Cerezyme one infusion every 2 weeks (Q2).		Patients receiving Cerezyme one infusion every 4 weeks(Q4).
All Cause Mortality
	Q2 Cerezyme		Q4 Cerezyme		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Q2 Cerezyme		Q4 Cerezyme		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/33 (21.2%)		4/62 (6.5%)		11/95 (11.6%)
Cardiac disorders
Cardiac failure congestive	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Eye disorders
Blindness	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Gastrointestinal disorders
Duodenitis	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Gastritis	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Injury, poisoning and procedural complications
Eye injury	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Fibula fracture	2/33 (6.1%)		0/62 (0%)		2/95 (2.1%)
Procedural hypotension	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Road traffic accident	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Tibia fracture	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Metabolism and nutrition disorders
Hyponatraemia	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Non-Hodgkin's lymphoma	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Nervous system disorders
Parkinson's disease	2/33 (6.1%)		0/62 (0%)		2/95 (2.1%)
Renal and urinary disorders
Renal failure	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Vascular disorders
Aortic dilatation	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Other (Not Including Serious) Adverse Events
	Q2 Cerezyme		Q4 Cerezyme		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/33 (60.6%)		51/62 (82.3%)		71/95 (74.7%)
Blood and lymphatic system disorders
Anaemia	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Splenic infarction	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Splenomegaly	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Thrombocytopenia	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Cardiac disorders
Cardiomegaly	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Palpitations	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Supraventricular tachycardia	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Congenital, familial and genetic disorders
Spondylolisthesis	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Ear and labyrinth disorders
Deafness bilateral	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Tinnitus	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Endocrine disorders
Hypothyroidism	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Eye disorders
Cataract	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Conjunctival haemorrhage	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Vision blurred	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Gastrointestinal disorders
Abdominal pain	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Abdominal pain upper	0/33 (0%)		3/62 (4.8%)		3/95 (3.2%)
Acquired oesophageal web	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Colonic polyp	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Constipation	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Diarrhoea	1/33 (3%)		2/62 (3.2%)		3/95 (3.2%)
Duodenitis	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Gastritis	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Gastrooesophageal reflux disease	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Inguinal hernia	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Nausea	1/33 (3%)		2/62 (3.2%)		3/95 (3.2%)
Oral mucosa erosion	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Stomach discomfort	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Vomiting	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
General disorders
Asthenia	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Fatigue	0/33 (0%)		6/62 (9.7%)		6/95 (6.3%)
Feeling hot	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Ill-defined disorder	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Infusion site erythema	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Infusion site pain	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Irritability	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Non-cardiac chest pain	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Oedema peripheral	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Pyrexia	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Immune system disorders
Hypersensitivity	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Multiple allergies	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Infections and infestations
Acariasis	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Bronchitis	0/33 (0%)		3/62 (4.8%)		3/95 (3.2%)
Bronchitis acute	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Cystitis	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Furuncle	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Gastroenteritis viral	0/33 (0%)		4/62 (6.5%)		4/95 (4.2%)
Influenza	0/33 (0%)		4/62 (6.5%)		4/95 (4.2%)
Laryngitis	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Nail bed infection	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Nasopharyngitis	1/33 (3%)		3/62 (4.8%)		4/95 (4.2%)
Otitis externa	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Otitis media	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Pneumonia	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Sinusitis	2/33 (6.1%)		5/62 (8.1%)		7/95 (7.4%)
Tinea versicolour	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Upper respiratory tract infection	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Urinary tract infection	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Wound infection	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Injury, poisoning and procedural complications
Arthropod bite	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Contusion	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Fall	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Foot fracture	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Hand fracture	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Joint dislocation	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Joint sprain	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Ligament rupture	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Meniscus lesion	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Mountain sickness acute	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Muscle strain	2/33 (6.1%)		0/62 (0%)		2/95 (2.1%)
Post-traumatic pain	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Procedural pain	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Spinal cord injury lumbar	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Tendon injury	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Tibia fracture	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Wrist fracture	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Investigations
Antibody test positive	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Blood pressure increased	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Breath sounds abnormal	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Cardiac murmur	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Computerised tomogram abdomen abnormal	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Haemoglobin decreased	0/33 (0%)		5/62 (8.1%)		5/95 (5.3%)
Platelet count decreased	0/33 (0%)		5/62 (8.1%)		5/95 (5.3%)
Prostatic specific antigen increased	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Weight increased	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
White blood cells urine positive	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Metabolism and nutrition disorders
Dehydration	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Fluid overload	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Folate deficiency	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Gout	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Hypercholesterolaemia	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Vitamin B12 deficiency	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/33 (9.1%)		10/62 (16.1%)		13/95 (13.7%)
Back pain	0/33 (0%)		10/62 (16.1%)		10/95 (10.5%)
Bone lesion	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Bone pain	2/33 (6.1%)		5/62 (8.1%)		7/95 (7.4%)
Flank pain	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Joint range of motion decreased	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Muscle spasms	3/33 (9.1%)		1/62 (1.6%)		4/95 (4.2%)
Muscular weakness	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Musculoskeletal pain	3/33 (9.1%)		4/62 (6.5%)		7/95 (7.4%)
Myalgia	1/33 (3%)		2/62 (3.2%)		3/95 (3.2%)
Neck pain	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Nodal osteoarthritis	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Osteoarthritis	2/33 (6.1%)		0/62 (0%)		2/95 (2.1%)
Osteopenia	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Pain in extremity	2/33 (6.1%)		5/62 (8.1%)		7/95 (7.4%)
Spinal column stenosis	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Weight bearing difficulty	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Lipoma	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Osteoma	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Skin cancer	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Uterine leiomyoma	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Nervous system disorders
Cervical root pain	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Cervicobrachial syndrome	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Dizziness	2/33 (6.1%)		1/62 (1.6%)		3/95 (3.2%)
Headache	2/33 (6.1%)		6/62 (9.7%)		8/95 (8.4%)
Hypoaesthesia	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Intention tremor	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Migraine	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Neuralgia	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Parkinson's disease	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Parkinsonian gait	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Sciatica	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Sinus headache	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Syncope vasovagal	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Tremor	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Psychiatric disorders
Affect lability	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Anxiety	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Depression	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Listless	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Renal and urinary disorders
Nephrolithiasis	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Renal cyst	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Urinary retention	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Urine flow decreased	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Reproductive system and breast disorders
Menorrhagia	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Ovarian cyst	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Polycystic ovaries	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Respiratory, thoracic and mediastinal disorders
Cough	1/33 (3%)		4/62 (6.5%)		5/95 (5.3%)
Dyspnoea	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Epistaxis	0/33 (0%)		2/62 (3.2%)		2/95 (2.1%)
Nasal congestion	1/33 (3%)		2/62 (3.2%)		3/95 (3.2%)
Pharyngeal erythema	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Pleural effusion	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Postnasal drip	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Rales	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Skin and subcutaneous tissue disorders
Acne	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Actinic keratosis	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Alopecia effluvium	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Dermal cyst	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Dry skin	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)
Ecchymosis	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Pruritus	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Rash	1/33 (3%)		1/62 (1.6%)		2/95 (2.1%)
Skin irritation	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Skin nodule	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Stasis dermatitis	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Urticaria	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Urticaria localised	1/33 (3%)		0/62 (0%)		1/95 (1.1%)
Vascular disorders
Hypertension	1/33 (3%)		3/62 (4.8%)		4/95 (4.2%)
Hypotension	0/33 (0%)		1/62 (1.6%)		1/95 (1.1%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

In multi-site studies, PI can publish after Genzyme publishes or 18 months after study completion. PI gives Genzyme a draft 60 days before publication. Genzyme can ask that confidential information be removed, and can defer publication another 60 days upon notifying PI that it will file a patent application on inventions contained in the draft.