The COMPASS Study: A Study of Volanesorsen (Formally ISIS-APOCIIIRx) in Patients With Hypertriglyceridemia

• Sponsor: Ionis Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02300233
• Collaborator: Akcea Therapeutics (Industry)
• Enrollment: 114
• Locations: 45
• Arms: 3
• Actual Duration (Months): 23.6
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 26 weeks in participants with Hypertriglyceridemia.

Condition or Disease	Intervention/Treatment	Phase
Hypertriglyceridemia	Drug: Volanesorsen; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The COMPASS Study: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients With Hypertriglyceridemia
• Actual Study Start Date: Feb 5, 2015
• Actual Primary Completion Date: Jul 27, 2016
• Actual Study Completion Date: Jan 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Drug: Placebo; Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.
Experimental: Volanesorsen 300 mg weekly Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks.	Drug: Volanesorsen; 300 mg volanesorsen administered subcutaneously once-weekly for 26 weeks.; Other Names: ISIS 304801
Experimental: Volanesorsen 300 mg biweekly, post Week 13 Volanesorsen 300 mg administered subcutaneously once-weekly for 13 weeks, then bi-weekly for 13 weeks.	Drug: Volanesorsen; 300 mg volanesorsen administered subcutaneously once-weekly for 26 weeks.; Other Names: ISIS 304801

Outcome Measures

Primary Outcome Measures

1. Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3 [Baseline to 3 months]

Secondary Outcome Measures

1. Absolute Change in Fasting TG From Baseline to Month 3 [Baseline to 3 months]

2. Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3 [Baseline to 3 months]

3. Percent Change in High-density Lipoprotein-cholesterol (HDL-C) From Baseline [Baseline to 3 months]

4. Treatment Response Rate Defined as Participants With Fasting TG < 150 mg/dL Reduction From Baseline at Month 3 [Baseline to 3 months]

   mg/dL = milligrams per deciliter

5. Change From Baseline in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) [Baseline to 3 and 6 months]

   HOMA-IR was calculated using the following formula: fasting insulin micro-international units per millimeter (μIU/mL) x fasting glucose mg/dL]/405. A negative change from baseline indicates improvement; a positive change from baseline indicates worsening.

6. Change From Baseline in Glycated Hemoglobin (HbA1c) in Type 2 Diabetes Mellitus (T2DM) Participants [Baseline to 3 and 6 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Body mass index (BMI) ≤ 45 kg/m2

2. Fasting Triglycerides (TG) ≥ 500 mg/dL (≥ 5.7 mmol/L) at Screening.

3. If on statin or fibrate, participants must be on stable, labeled dose for at least 3 months prior to screening. Participants not receiving these drugs within 4 weeks prior to screening are also eligible.

Exclusion Criteria:

1. Type 1 diabetes mellitus

2. Newly diagnosed type 2 diabetes mellitus (within 12 weeks of screening) or HbA1c ≥ 9.0% at Screening

3. Acute pancreatitis within 3 months of screening

4. Acute Coronary Syndrome within 6 months of screening

5. Major surgery within 3 months of screening

6. Prior exposure to ISIS 304801

7. Have any other conditions in the opinion of the investigator which could interfere with the participant participating in or completing the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IONIS Investigative Site	Encinitas	California	United States	92024
2	IONIS Investigative Site	San Francisco	California	United States	94143
3	IONIS Investigative Site	Boca Raton	Florida	United States	33434
4	IONIS Investigative Site	Miami	Florida	United States	33147
5	IONIS Investigative Site	Sterling	Illinois	United States	61081
6	IONIS Investigative Site	Kansas City	Kansas	United States	66160
7	IONIS Investigative Site	Salisbury	Maryland	United States	73103
8	IONIS Investigative Site	Towson	Maryland	United States	21204
9	IONIS Investigative Site	Boston	Massachusetts	United States	02114
10	IONIS Investigative Site	Grandville	Michigan	United States	49418
11	IONIS Investigative Site	North Massapequa	New York	United States	11758-1802
12	IONIS Investigative Site	Benson	North Carolina	United States	27504
13	IONIS Investigative Site	Chapel Hill	North Carolina	United States	27609
14	IONIS Investigative Site	Farmville	North Carolina	United States	27828
15	IONIS Investigative Site	Greenville	North Carolina	United States	27834
16	IONIS Investigative Site	Morrisville	North Carolina	United States	27560
17	IONIS Investigative Site	Raleigh	North Carolina	United States	27612
18	IONIS Investigative Site	Wilson	North Carolina	United States	27609
19	IONIS Investigative Site	Wilson	North Carolina	United States	27893
20	IONIS Investigative Site	Cincinnati	Ohio	United States	45227
21	IONIS Investigative Site	Kettering	Ohio	United States	45429
22	IONIS Investigative Site	Marion	Ohio	United States	43302
23	IONIS Investigative Site	Oklahoma City	Oklahoma	United States	73103
24	IONIS Investigative Site	Portland	Oregon	United States	97239
25	IONIS Investigative Site	Providence	Rhode Island	United States	02906
26	IONIS Investigative Site	Houston	Texas	United States	77030
27	IONIS Investigative Site	Salt Lake City	Utah	United States	84108
28	IONIS Investigative Site	Norfolk	Virginia	United States	23510
29	IONIS Investigative Site	Seattle	Washington	United States	98104
30	IONIS Investigative Site	Vancouver	British Columbia	Canada	V6Z 1Y6
31	IONIS Investigative Site	London	Ontario	Canada	N6A 5B7
32	IONIS Investigative Site	Chicoutimi	Quebec	Canada	G7H 7K9
33	IONIS Investigative Site	Sainte-Foy	Quebec	Canada	G1V 4M6
34	IONIS Investigative Site	Dijon		France	21079
35	IONIS Investigative Site	Marseille		France	13385
36	IONIS Investigative Site	Paris		France	75013
37	IONIS Investigative Site	Saint Herblain		France
38	IONIS Investigative Site	Koeln	North Rhine-Westphalia	Germany	50937
39	IONIS Investigative Site	Berlin		Germany	13353
40	IONIS Investigative Site	Dresden		Germany	01307
41	IONIS Investigative Site	Amsterdam	North Holland	Netherlands	1105 AZ
42	IONIS Investigative Site	Rotterdam	South Holland	Netherlands	3045 PM
43	IONIS Investigative Site	Utrecht		Netherlands	3584 CX
44	IONIS Investigative Site	Manchester		United Kingdom	M23 9LT
45	IONIS Investigative Site	Peterborough		United Kingdom	PE3 6DA

Sponsors and Collaborators

• Ionis Pharmaceuticals, Inc.
• Akcea Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ionis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02300233
• Other Study ID Numbers: ISIS 304801-CS16; 2014-003434-93
• First Posted: Nov 24, 2014
• Last Update Posted: Apr 13, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hypertriglyceridemia

Study Results

Participant Flow

Recruitment Details	A total of 114 participants were randomized at multiple study centers worldwide.
Pre-assignment Detail	114 participants were randomized, and 113 received study drug. One patient was randomized, but discontinued before dosing, and thus included only in the volanesorsen Total (Not public) column. The study included a ≤ 8-week screening period (including a diet-stabilization period), a 26-week treatment period, and a 13-week post-treatment evaluation period.

Arm/Group Title	Placebo	Volanesorsen 300 mg Weekly	Volanesorsen 300 mg Biweekly, Post Week 13
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 13 weeks, then bi-weekly for 13 weeks.
Period Title: Overall Study
STARTED	38	25	50
COMPLETED	34	24	27
NOT COMPLETED	4	1	23

Baseline Characteristics

Arm/Group Title	Placebo	Volanesorsen 300 mg Weekly	Volanesorsen 300 mg Biweekly, Post Week 13	Total
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 13 weeks, then bi-weekly for 13 weeks.	Total of all reporting groups
Overall Participants	38	25	50	113
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (10)	50 (9)	51 (11)	51 (10)
Sex: Female, Male (Count of Participants)
Female	8 21.1%	5 20%	14 28%	27 23.9%
Male	30 78.9%	20 80%	36 72%	86 76.1%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	1 2.6%	1 4%	0 0%	2 1.8%
Not Hispanic or Latino	37 97.4%	24 96%	50 100%	111 98.2%
Race/Ethnicity, Customized (Count of Participants)
White	33 86.8%	25 100%	47 94%	105 92.9%
Asian	3 7.9%	0 0%	1 2%	4 3.5%
American Indian or Alaskan Native	0 0%	0 0%	1 2%	1 0.9%
Other Race	1 2.6%	0 0%	1 2%	2 1.8%
Multiple	1 2.6%	0 0%	0 0%	1 0.9%
Fasting Triglycerides (milligrams per deciliter (mg/dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams per deciliter (mg/dL)]	1414 (1253)	1046 (560)	1251 (838)	1261 (955)

Outcome Measures

1. Primary Outcome

Title	Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.

Arm/Group Title	Placebo	Volanesorsen Total
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks; or once-weekly for 13 weeks, then bi-weekly for 13 weeks.
Measure Participants	38	75
Least Squares Mean (95% Confidence Interval) [percent change]	-0.9	-71.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Volanesorsen Total
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Mean (LSM)
	Estimated Value	-70.3
	Confidence Interval	(2-Sided) 95%; -85.4 to -55.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Absolute Change in Fasting TG From Baseline to Month 3
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

The FAS included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment. Volanesorsen 300 mg biweekly group includes patients who received weekly dosing in first 13 weeks, and then bi-weekly for 13 weeks. For month 3 assessments, the results were combined since all patients were on weekly dosing. And for month 6 assessments, the results were split to show the results in each dosing group.

Arm/Group Title	Placebo	Volanesorsen Total
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks; or once-weekly for 13 weeks, then bi-weekly for 13 weeks.
Measure Participants	38	75
Least Squares Mean (95% Confidence Interval) [mg/dL]	74	-869

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Volanesorsen Total
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LSM
	Estimated Value	-943
	Confidence Interval	(2-Sided) 95%; -1197 to -689
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

The FAS included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.

Arm/Group Title	Placebo	Volanesorsen Total
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks; or once-weekly for 13 weeks, then bi-weekly for 13 weeks.
Measure Participants	38	75
Count of Participants [Participants]	5 13.2%	65 260%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Volanesorsen Total
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	96.02
	Confidence Interval	(2-Sided) 95%; 19.71 to 467.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percent Change in High-density Lipoprotein-cholesterol (HDL-C) From Baseline
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

The FAS included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.

Arm/Group Title	Placebo	Volanesorsen Total
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks; or once-weekly for 13 weeks, then bi-weekly for 13 weeks.
Measure Participants	38	75
Least Squares Mean (95% Confidence Interval) [percent change]	4.4	61.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Volanesorsen Total
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LSM
	Estimated Value	56.8
	Confidence Interval	(2-Sided) 95%; 45.1 to 68.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Treatment Response Rate Defined as Participants With Fasting TG < 150 mg/dL Reduction From Baseline at Month 3
Description	mg/dL = milligrams per deciliter
Time Frame	Baseline to 3 months

Outcome Measure Data

Analysis Population Description

The FAS included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment.

Arm/Group Title	Placebo	Volanesorsen Total
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks; or once-weekly for 13 weeks, then bi-weekly for 13 weeks.
Measure Participants	38	75
Count of Participants [Participants]	0 0%	11 44%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Volanesorsen Total
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0474
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	14.93
	Confidence Interval	(2-Sided) 95%; 1.03 to 215.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR)
Description	HOMA-IR was calculated using the following formula: fasting insulin micro-international units per millimeter (μIU/mL) x fasting glucose mg/dL]/405. A negative change from baseline indicates improvement; a positive change from baseline indicates worsening.
Time Frame	Baseline to 3 and 6 months

Outcome Measure Data

Analysis Population Description

The FAS included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment. Number analyzed were the participants evaluated at the given time point.

Arm/Group Title	Placebo	Volanesorsen 300 mg Weekly	Volanesorsen 300 mg Biweekly, Post Week 13
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 13 weeks, then bi-weekly for 13 weeks.
Measure Participants	38	25	50
Month 3	-0.29 (3.12)	1.53 (4.89)	-0.45 (4.97)
Month 6	-0.37 (3.18)	1.54 (7.69)	0.56 (2.97)

7. Secondary Outcome

Title	Change From Baseline in Glycated Hemoglobin (HbA1c) in Type 2 Diabetes Mellitus (T2DM) Participants
Time Frame	Baseline to 3 and 6 months

Outcome Measure Data

Analysis Population Description

The FAS included all participants who were randomized, received at least one dose of study drug, and had a baseline TG assessment. Number analyzed were the T2DM participants evaluated at the given time point.

Arm/Group Title	Placebo	Volanesorsen 300 mg Weekly	Volanesorsen 300 mg Biweekly, Post Week 13
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks.	Volanesorsen 300 mg administered subcutaneously once-weekly for 13 weeks, then bi-weekly for 13 weeks.
Measure Participants	14	9	21
Month 3	-0.0 (0.5)	0.4 (0.6)	0.1 (0.5)
Month 6	-0.2 (0.6)	0.8 (0.9)	0.3 (0.9)

Adverse Events

Time Frame	Up to approximately 39 weeks.
Adverse Event Reporting Description	The safety set included all randomized participants who received at least one dose of study drug.
Arm/Group Title	Placebo		Volanesorsen 300 mg Weekly		Volanesorsen 300 mg Biweekly, Post Week 13
Arm/Group Description	Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.		Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks.		Volanesorsen 300 mg administered subcutaneously once-weekly for 13 weeks, then bi-weekly for 13 weeks.
All Cause Mortality
	Placebo		Volanesorsen 300 mg Weekly		Volanesorsen 300 mg Biweekly, Post Week 13
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/25 (0%)		0/50 (0%)
Serious Adverse Events
	Placebo		Volanesorsen 300 mg Weekly		Volanesorsen 300 mg Biweekly, Post Week 13
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/38 (10.5%)		2/25 (8%)		6/50 (12%)
Ear and labyrinth disorders
Vertigo	0/38 (0%)		0/25 (0%)		1/50 (2%)
Gastrointestinal disorders
Ileus paralytic	1/38 (2.6%)		0/25 (0%)		0/50 (0%)
Pancreatitis acute	2/38 (5.3%)		1/25 (4%)		0/50 (0%)
Pancreatitis relapsing	1/38 (2.6%)		0/25 (0%)		0/50 (0%)
Small intestinal obstruction	0/38 (0%)		0/25 (0%)		1/50 (2%)
General disorders
Non-cardiac chest pain	0/38 (0%)		0/25 (0%)		1/50 (2%)
Hepatobiliary disorders
Cholelithiasis	1/38 (2.6%)		0/25 (0%)		0/50 (0%)
Immune system disorders
Serum sickness	0/38 (0%)		0/25 (0%)		1/50 (2%)
Infections and infestations
Pancreas infection	1/38 (2.6%)		0/25 (0%)		0/50 (0%)
Injury, poisoning and procedural complications
Ulna fracture	0/38 (0%)		1/25 (4%)		0/50 (0%)
Nervous system disorders
Carotid artery stenosis	0/38 (0%)		0/25 (0%)		1/50 (2%)
Hemiparesis	0/38 (0%)		0/25 (0%)		1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/38 (2.6%)		0/25 (0%)		0/50 (0%)
Vascular disorders
Hypertensive crisis	0/38 (0%)		0/25 (0%)		1/50 (2%)
Peripheral arterial occlusive disease	0/38 (0%)		0/25 (0%)		1/50 (2%)
Other (Not Including Serious) Adverse Events
	Placebo		Volanesorsen 300 mg Weekly		Volanesorsen 300 mg Biweekly, Post Week 13
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/38 (81.6%)		24/25 (96%)		49/50 (98%)
Blood and lymphatic system disorders
Thrombocytopenia	2/38 (5.3%)		2/25 (8%)		8/50 (16%)
Anaemia	2/38 (5.3%)		2/25 (8%)		2/50 (4%)
Ear and labyrinth disorders
Vertigo	2/38 (5.3%)		0/25 (0%)		0/50 (0%)
Gastrointestinal disorders
Diarrhoea	4/38 (10.5%)		5/25 (20%)		5/50 (10%)
Abdominal pain	1/38 (2.6%)		1/25 (4%)		9/50 (18%)
Nausea	1/38 (2.6%)		1/25 (4%)		6/50 (12%)
Vomiting	1/38 (2.6%)		1/25 (4%)		4/50 (8%)
Abdominal pain upper	3/38 (7.9%)		0/25 (0%)		2/50 (4%)
Dry mouth	0/38 (0%)		1/25 (4%)		3/50 (6%)
General disorders
Injection site erythema	2/38 (5.3%)		23/25 (92%)		38/50 (76%)
Injection site pain	2/38 (5.3%)		10/25 (40%)		29/50 (58%)
Injection site swelling	1/38 (2.6%)		12/25 (48%)		24/50 (48%)
Injection site pruritus	0/38 (0%)		10/25 (40%)		17/50 (34%)
Injection site discolouration	0/38 (0%)		12/25 (48%)		11/50 (22%)
Injection site induration	2/38 (5.3%)		7/25 (28%)		11/50 (22%)
Injection site discomfort	1/38 (2.6%)		2/25 (8%)		11/50 (22%)
Fatigue	4/38 (10.5%)		2/25 (8%)		7/50 (14%)
Injection site bruising	1/38 (2.6%)		1/25 (4%)		10/50 (20%)
Injection site rash	0/38 (0%)		3/25 (12%)		6/50 (12%)
Pyrexia	2/38 (5.3%)		2/25 (8%)		5/50 (10%)
Injection site reaction	0/38 (0%)		4/25 (16%)		4/50 (8%)
Injection site warmth	0/38 (0%)		2/25 (8%)		6/50 (12%)
Asthenia	2/38 (5.3%)		3/25 (12%)		2/50 (4%)
Injection site haemorrhage	0/38 (0%)		2/25 (8%)		5/50 (10%)
Injection site hypoaesthesia	0/38 (0%)		1/25 (4%)		5/50 (10%)
Injection site inflammation	1/38 (2.6%)		2/25 (8%)		2/50 (4%)
Pain	2/38 (5.3%)		0/25 (0%)		2/50 (4%)
Injection site mass	0/38 (0%)		2/25 (8%)		1/50 (2%)
Injection site oedema	0/38 (0%)		0/25 (0%)		3/50 (6%)
Hepatobiliary disorders
Hepatic pain	0/38 (0%)		2/25 (8%)		0/50 (0%)
Infections and infestations
Nasopharyngitis	5/38 (13.2%)		8/25 (32%)		4/50 (8%)
Bronchitis	3/38 (7.9%)		1/25 (4%)		3/50 (6%)
Upper respiratory tract infection	2/38 (5.3%)		2/25 (8%)		2/50 (4%)
Urinary tract infection	2/38 (5.3%)		2/25 (8%)		0/50 (0%)
Influenza	2/38 (5.3%)		0/25 (0%)		1/50 (2%)
Injury, poisoning and procedural complications
Contusion	1/38 (2.6%)		2/25 (8%)		1/50 (2%)
Investigations
Red blood cell sedimentation rate increased	4/38 (10.5%)		6/25 (24%)		5/50 (10%)
C-reactive protein increased	0/38 (0%)		3/25 (12%)		5/50 (10%)
Low density lipoprotein increased	0/38 (0%)		3/25 (12%)		4/50 (8%)
Platelet count decreased	2/38 (5.3%)		1/25 (4%)		2/50 (4%)
Hepatic enzyme increased	0/38 (0%)		1/25 (4%)		3/50 (6%)
Blood creatinine increased	0/38 (0%)		0/25 (0%)		3/50 (6%)
Metabolism and nutrition disorders
Diabetes mellitus	0/38 (0%)		1/25 (4%)		3/50 (6%)
Gout	2/38 (5.3%)		1/25 (4%)		1/50 (2%)
Type 2 diabetes mellitus	2/38 (5.3%)		2/25 (8%)		0/50 (0%)
Decreased appetite	0/38 (0%)		2/25 (8%)		0/50 (0%)
Musculoskeletal and connective tissue disorders
Back pain	4/38 (10.5%)		4/25 (16%)		8/50 (16%)
Arthralgia	0/38 (0%)		2/25 (8%)		7/50 (14%)
Pain in extremity	1/38 (2.6%)		2/25 (8%)		5/50 (10%)
Myalgia	0/38 (0%)		2/25 (8%)		4/50 (8%)
Nervous system disorders
Headache	4/38 (10.5%)		2/25 (8%)		5/50 (10%)
Dizziness	2/38 (5.3%)		2/25 (8%)		2/50 (4%)
Psychiatric disorders
Depression	0/38 (0%)		2/25 (8%)		3/50 (6%)
Renal and urinary disorders
Albuminuria	0/38 (0%)		2/25 (8%)		1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Cough	3/38 (7.9%)		0/25 (0%)		2/50 (4%)
Skin and subcutaneous tissue disorders
Erythema	0/38 (0%)		2/25 (8%)		2/50 (4%)
Rash	0/38 (0%)		3/25 (12%)		0/50 (0%)
Actinic keratosis	2/38 (5.3%)		0/25 (0%)		0/50 (0%)
Dermatitis	0/38 (0%)		2/25 (8%)		0/50 (0%)
Vascular disorders
Hot flush	2/38 (5.3%)		0/25 (0%)		1/50 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.