Trial Outcomes & Findings for Efficacy Study of DiaPep277 in Newly Diagnosed Type 1 Diabetes Patients (NCT NCT00615264)

Last Updated: 2016-06-06

Results Overview

Beta-cell function, measured as change in stimulated C-peptide secretion measured 0, 2, 6, 10 and 20 minutes post administration \[area under the curve (AUC), 0-20 minutes\] at Baseline and 24 months, during a glucagon stimulation test (GST). The change in AUC was calculated per patient by subtracting the baseline AUC from the 24 month AUC.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

457 participants

Primary outcome timeframe

Baseline and 24 months

Results posted on

2016-06-06

Participant Flow

Participant milestones

Participant milestones
Measure	DiaPep277 DiaPep277 1.0 mg + 40 mg Mannitol in 0.5 mL lipid emulsion. DiaPep277: 1.0 mg dose, administered as subcutaneous injection, on 0, 1, 3, 6, 9, 12, 15, 18 and 21 months	Placebo Mannitol 40 mg in 0.5 mL lipid emulsion. Placebo: Mannitol (excipient) 40 mg, administered as subcutaneous injection on 1, 3, 6, 9, 12, 15, 18 and 21 months.
Overall Study STARTED	225	232
Overall Study Received at Least One Dose (ITT)	225	231
Overall Study ITT Patients Who Met Inc/Excl (MITT)	209	213
Overall Study COMPLETED	175	180
Overall Study NOT COMPLETED	50	52

Reasons for withdrawal

Reasons for withdrawal
Measure	DiaPep277 DiaPep277 1.0 mg + 40 mg Mannitol in 0.5 mL lipid emulsion. DiaPep277: 1.0 mg dose, administered as subcutaneous injection, on 0, 1, 3, 6, 9, 12, 15, 18 and 21 months	Placebo Mannitol 40 mg in 0.5 mL lipid emulsion. Placebo: Mannitol (excipient) 40 mg, administered as subcutaneous injection on 1, 3, 6, 9, 12, 15, 18 and 21 months.
Overall Study Withdrawal by Subject	17	19
Overall Study Lost to Follow-up	6	13
Overall Study Adverse Event	8	5
Overall Study Death	1	1
Overall Study Protocol Violation	11	7
Overall Study Not defined	7	4
Overall Study Dermal Hypersensitivity	0	3

Baseline Characteristics

Efficacy Study of DiaPep277 in Newly Diagnosed Type 1 Diabetes Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DiaPep277 n=225 Participants DiaPep277 1.0 mg + 40 mg Mannitol in 0.5mL Lipid emulsion. DiaPep277: 1.0 mg dose, administered as subcutaneous injection, on 0, 1, 3, 6, 9, 12, 15, 18 and 21 months	Placebo n=231 Participants Mannitol 40 mg in 0.5 mL Lipid emulsion. Placebo: Mannitol (excipient) 40 mg, administered as subcutaneous injection on 1, 3, 6, 9, 12, 15, 18 and 21 months.	Total n=456 Participants Total of all reporting groups
Age, Continuous	26.6 years STANDARD_DEVIATION 7.99 • n=5 Participants	26.4 years STANDARD_DEVIATION 7.85 • n=7 Participants	26.5 years STANDARD_DEVIATION 7.91 • n=5 Participants
Age, Customized	25.0 years n=5 Participants	26.0 years n=7 Participants	25.0 years n=5 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	73 Participants n=7 Participants	156 Participants n=5 Participants
Sex: Female, Male Male	142 Participants n=5 Participants	158 Participants n=7 Participants	300 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	212 participants n=5 Participants	212 participants n=7 Participants	424 participants n=5 Participants
Race/Ethnicity, Customized Black	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants
Race/Ethnicity, Customized Oriental	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized Other	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 months

Population: Modified Intent to Treat (MITT) Population - all randomized patients who received at least one dose of study medication and who entered the study according to the definition of the target population, as defined by the inclusion and exclusion criteria in the study protocol

Outcome measures

Outcome measures
Measure	DiaPep277 n=209 Participants DiaPep277 1.0 mg + 40 mg Mannitol in 0.5 mL lipid emulsion. DiaPep277: 1.0 mg dose, administered as subcutaneous injection, on 0, 1, 3, 6, 9, 12, 15, 18 and 21 months	Placebo n=213 Participants Mannitol 40 mg in 0.5 mL lipid emulsion. Placebo: Mannitol (excipient) 40 mg, administered as subcutaneous injection on 1, 3, 6, 9, 12, 15, 18 and 21 months.
Change From Baseline in Glucagon-stimulated C-peptide AUC at 24 Months	-3.848 nmol*minute/L Standard Error 0.4666	-4.348 nmol*minute/L Standard Error 0.4584

SECONDARY outcome

Timeframe: Baseline and 24 Months

Population: Modified Intent to Treat (MITT) Population

Beta cell function, measured as stimulated C-peptide secretion from 0 to 120 min post administration AUC, at baseline and 24 month measurements in a mixed-meal tolerance test (MMTT). The change in AUC was calculated per patient by subtracting the baseline AUC from the 24 month AUC.

Outcome measures

Outcome measures
Measure	DiaPep277 n=209 Participants DiaPep277 1.0 mg + 40 mg Mannitol in 0.5 mL lipid emulsion. DiaPep277: 1.0 mg dose, administered as subcutaneous injection, on 0, 1, 3, 6, 9, 12, 15, 18 and 21 months	Placebo n=213 Participants Mannitol 40 mg in 0.5 mL lipid emulsion. Placebo: Mannitol (excipient) 40 mg, administered as subcutaneous injection on 1, 3, 6, 9, 12, 15, 18 and 21 months.
Change From Baseline in Mixed-meal Stimulated C-peptide AUC at 24 Months	-44.33 nmol*minute/L Standard Error 3.6884	-43.24 nmol*minute/L Standard Error 3.5898

Adverse Events

DiaPep277

Serious events: 26 serious events

Other events: 173 other events

Deaths: 0 deaths

Placebo

Serious events: 14 serious events

Other events: 164 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Jeanne Novak

CBR International

Phone: 7207461190

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator shall submit any paper or presentation to the Sponsor for review and comments at least 60 days prior to submitting the same to a third party. Upon receiving any request from the Sponsor to delete any Confidential Information or request to delay in publication up to 90 days to allow the filing of any Sponsor application, the Investigator shall take the request action. Investigator shall not be restricted after 18 months from completion of their site's performance in the study.
Publication restrictions are in place

Restriction type: OTHER

Measure	DiaPep277 n=225 participants at risk DiaPep277 1.0 mg + 40 mg Mannitol in 0.5 mL lipid emulsion. DiaPep277: 1.0 mg dose, administered as subcutaneous injection, on 0, 1, 3, 6, 9, 12, 15, 18 and 21 months	Placebo n=231 participants at risk Mannitol 40 mg in 0.5 mL lipid emulsion. Placebo: Mannitol (excipient) 40 mg, administered as subcutaneous injection on 1, 3, 6, 9, 12, 15, 18 and 21 months.
Metabolism and nutrition disorders Diabetic Ketoacidosis	1.8% 4/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.87% 2/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Metabolism and nutrition disorders Hypoglycaemia	0.89% 2/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.87% 2/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Psychiatric disorders Accidental Overdose	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Metabolism and nutrition disorders Hypoglycemic Coma	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Psychiatric disorders Major Depression	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Metabolism and nutrition disorders Hyperglycemia	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Metabolism and nutrition disorders Type 1 Diabetes Mellitus	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Psychiatric disorders Alcohol Poisoning	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Musculoskeletal and connective tissue disorders Jaw Fracture	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Injury, poisoning and procedural complications Laceration	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Musculoskeletal and connective tissue disorders Wrist Fracture	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Nervous system disorders Concussion	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Nervous system disorders Head Injury	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Musculoskeletal and connective tissue disorders Ligament Rupture	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Bronchopneumomnia	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Gastrointestinal disorders Diverticulitis	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Gastrointestinal disorders Gastritis Viral	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Infection	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Influenza	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Gastrointestinal disorders Gastroenteritis	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Urinary Tract Infection	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Nervous system disorders Facial Paresis	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Nervous system disorders Loss of Consciousness	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Nervous system disorders Migraine	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Psychiatric disorders Mental Disorder	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Hepatobiliary disorders Cholelithiasis	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Hepatobiliary disorders Hepatitis	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Renal and urinary disorders Nephrolithiasis	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Renal and urinary disorders Renal Colic	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Respiratory, thoracic and mediastinal disorders Nasal Septum Deviation	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Skin and subcutaneous tissue disorders Erythema Nodosum	0.44% 1/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.00% 0/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Skin and subcutaneous tissue disorders Henoch-Schonlein Purpura	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Skin and subcutaneous tissue disorders Urticaria Cholinergic	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Social circumstances Death	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Blood and lymphatic system disorders Neutropenia	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)

Measure	DiaPep277 n=225 participants at risk DiaPep277 1.0 mg + 40 mg Mannitol in 0.5 mL lipid emulsion. DiaPep277: 1.0 mg dose, administered as subcutaneous injection, on 0, 1, 3, 6, 9, 12, 15, 18 and 21 months	Placebo n=231 participants at risk Mannitol 40 mg in 0.5 mL lipid emulsion. Placebo: Mannitol (excipient) 40 mg, administered as subcutaneous injection on 1, 3, 6, 9, 12, 15, 18 and 21 months.
Infections and infestations Nasopharyngitis	16.4% 37/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	17.7% 41/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Influenza	13.3% 30/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	10.0% 23/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Upper respiratory Tract Infection	10.2% 23/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	8.2% 19/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Gastroenteritis	6.2% 14/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	7.4% 17/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Pharyngitis	3.6% 8/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.0% 7/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Tonsillitis	3.1% 7/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	2.6% 6/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Urinary Tract Infection	2.7% 6/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.9% 9/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Bronchitis	2.7% 6/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.5% 8/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Sinusitis	2.7% 6/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.5% 8/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Cystitis	2.7% 6/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Infections and infestations Respiratory Tract Infection	2.2% 5/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	2.6% 6/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Gastrointestinal disorders Nausea	3.6% 8/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	2.6% 6/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Gastrointestinal disorders Gastritis	3.6% 8/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	1.3% 3/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Gastrointestinal disorders Toothache	3.1% 7/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	1.3% 3/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Gastrointestinal disorders Diarrhea	3.1% 7/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.87% 2/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Gastrointestinal disorders Vomiting	2.2% 5/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.0% 7/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Gastrointestinal disorders Abdominal Pain Upper	1.3% 3/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	2.2% 5/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
General disorders Pyrexia	4.4% 10/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	4.8% 11/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
General disorders Injection Site Erythema	4.0% 9/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	1.3% 3/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
General disorders Injection Site Pain	3.6% 8/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.5% 8/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
General disorders Injection Site Induration	2.2% 5/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	1.3% 3/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Injury, poisoning and procedural complications Injury, Poisoning and Procedural Complications	12.4% 28/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	8.2% 19/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Investigations Blood Creatine Phosphokinase Increased	2.7% 6/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.9% 9/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Investigations Alanine Aminotransferase Increased	2.2% 5/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	1.3% 3/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Investigations Glycosylated Haemoglobin Increased	1.3% 3/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.0% 7/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Skin and subcutaneous tissue disorders Skin and Subcutaneous Tissue Disorders	11.6% 26/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	9.1% 21/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Musculoskeletal and connective tissue disorders Back Pain	4.4% 10/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.9% 9/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Nervous system disorders Headache	5.3% 12/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	5.2% 12/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Nervous system disorders Dizziness	2.2% 5/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.43% 1/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Respiratory, thoracic and mediastinal disorders Respiratory, Thoracic and Mediastinal Disorders	6.2% 14/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	6.1% 14/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Metabolism and nutrition disorders Hypercholesterolemia	0.89% 2/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.0% 7/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Renal and urinary disorders Renal and Urinary Disorders	4.4% 10/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	1.7% 4/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Reproductive system and breast disorders Reproductive System and Breast Disorders	3.6% 8/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.0% 7/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Psychiatric disorders Psychiatric disorders	3.6% 8/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	2.6% 6/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Endocrine disorders Endocrine Disorders	3.1% 7/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	0.87% 2/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Eye disorders Eye Disorders	2.7% 6/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	2.2% 5/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Blood and lymphatic system disorders Anemia	0.89% 2/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	2.2% 5/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Vascular disorders Hypertension	1.3% 3/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	2.6% 6/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Immune system disorders Immune System Disorders	1.3% 3/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	2.6% 6/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)
Cardiac disorders Cardiac Disorders	0.00% 0/225 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)	3.9% 9/231 • AE data were collected from the time of subject enrollment through three months after the final product administrations (Total of 24 months after first study product administration)