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Trial record 7 of 9 for:    otelixizumab

Trial of Otelixizumab for Adults With Newly Diagnosed Type 1 Diabetes Mellitus (Autoimmune): DEFEND-1 (DEFEND-1)

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ClinicalTrials.gov Identifier: NCT00678886
Recruitment Status : Completed
First Posted : May 16, 2008
Results First Posted : October 3, 2017
Last Update Posted : October 3, 2017
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 1
Interventions Biological: otelixizumab infusion plus physician determined standard of care
Biological: placebo infusion plus physician determined standard of care
Enrollment 272

Recruitment Details This study was conducted at 85 centers in 9 countries namely Canada (4), Germany (3), Denmark (1), Spain (5), Finland (2), United Kingdom (4), Italy (8), Sweden (11) and United States of America (47) from 29 July 2008 to 31 January 2012. A total of 240 participants with new-onset Type 1 diabetes mellitus (NOT1DM) were planned to be enrolled.
Pre-assignment Details Participants were screened for a period of 35 days and a total of 272 participants were randomized in the study.
Arm/Group Title Adolescent (Placebo) Adolescent (Otelixizumab) Adult (Placebo) Adult (Otelixizumab)
Hide Arm/Group Description Eligible adolescent participants received matching placebo to Otelixizumab administered as intravenous (IV) infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose. Eligible adolescent participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 milligram [mg], second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose. Eligible adult participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive Days. Participants were followed-up for 24 months after the last dose. Eligible adult participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg), second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Period Title: Overall Study
Started 10 19 81 162
Completed 10 19 72 153
Not Completed 0 0 9 9
Reason Not Completed
Withdrawal by Subject             0             0             4             6
Physician Decision             0             0             1             1
Lost to Follow-up             0             0             3             2
Other             0             0             1             0
Arm/Group Title Placebo Otelixizumab Total
Hide Arm/Group Description Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose. Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose. Total of all reporting groups
Overall Number of Baseline Participants 91 181 272
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 91 participants 181 participants 272 participants
25.2  (7.13) 24.7  (6.54) 24.9  (6.73)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 181 participants 272 participants
Female
31
  34.1%
64
  35.4%
95
  34.9%
Male
60
  65.9%
117
  64.6%
177
  65.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 181 participants 272 participants
American Indian or Alaska Native
0
   0.0%
1
   0.6%
1
   0.4%
Asian
2
   2.2%
1
   0.6%
3
   1.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   2.2%
6
   3.3%
8
   2.9%
White
85
  93.4%
169
  93.4%
254
  93.4%
More than one race
2
   2.2%
4
   2.2%
6
   2.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12
Hide Description Mixed meal-stimulated C-peptide AUC was the area under the C-peptide/time curve from Time 0 to 120 minutes, calculated using the trapezoidal rule. This reported AUC was normalized for time interval by dividing it by 120 minutes. This normalized AUC was calculated for each participant at Baseline, Week 12, and at Months 6, 12, 18, and 24. Data has been presented for meal stimulated C-peptide Area under assessment performed at Month 12. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Month 12.
Time Frame Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population, comprised of all participants who were randomized and received any part of at least 1 infusion of study drug.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Least Squares Mean (Standard Error)
Unit of Measure: nanomoles per liter
-0.21  (0.030) -0.21  (0.021)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Mixed meal-stimulated C-peptide AUC, Placebo Vs Otelixizumab at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.813
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.06 to 0.08
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12
Hide Description A participant was considered a responder if, at the given time point, the participant had HbA1c<= 6.5%, and mean daily insulin use over 7 consecutive days < 0.5 international units per kilogram per day (IU/kg/day) during the 2 weeks preceding the visit. Data has been presented from number of participants with their percentages who were responders at Week 12 and Months 6 and 12.
Time Frame Week 12 and Months 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Measure Type: Count of Participants
Unit of Measure: Participants
Responders at Week 12 Number Analyzed 78 participants 161 participants
45
  57.7%
85
  52.8%
Responders at Month 6 Number Analyzed 76 participants 158 participants
42
  55.3%
74
  46.8%
Responders at Month 12 Number Analyzed 80 participants 160 participants
34
  42.5%
56
  35.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Percentage of responders, Placebo Vs Otelixizumab at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.737
Comments [Not Specified]
Method Hochberg adjusted
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.47 to 1.70
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Percentage of responders, Placebo Vs Otelixizumab at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.737
Comments [Not Specified]
Method Hochberg adjusted
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.42 to 1.39
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Percentage of responders, Placebo Vs Otelixizumab at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.481
Comments [Not Specified]
Method Hochberg adjusted
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.45 to 1.46
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Daily Insulin Use at Week 12 and Months 6 and 12.
Hide Description Participants recorded their daily insulin use in their electronic diaries. In particular, insulin was recorded thoroughly and accurately for at least 7 consecutive days during the 2 weeks before the visits at Baseline, Week 12, and Months 6 and 12. During each of these visits, the investigator/designee accessed the invivodata DiaryPRO web site to review insulin-use data for the previous 2-week period to ensure completeness. If errors/gaps were identified (e.g., if the participant did not take insulin and not entered 0 units), the investigator/designee recorded the missing data from participant recall using a data clarification form (DCF). Paper diary to collect insulin use, were reviewed for completeness. Any missing data that could be recalled by the participant was entered. If the participant did not record any insulin use during the 2-week period before the visit, the site obtained an insulin use history for the previous 7 days and calculated the average daily insulin dose.
Time Frame Week 12 and Months 6 and 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Least Squares Mean (Standard Error)
Unit of Measure: IU/kg
Mean daily insulin use at Week 12 0.34  (0.017) 0.31  (0.013)
Mean daily insulin use at Month 6 0.36  (0.022) 0.36  (0.016)
Mean daily insulin use at Month 12 0.42  (0.023) 0.39  (0.017)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Mean insulin use, Placebo Vs Otelixizumab at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.281
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.07 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Mean insulin use, Placebo Vs Otelixizumab at Month 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.969
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.05 to 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Mean insulin use, Placebo Vs Otelixizumab at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.272
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.08 to 0.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title HbA1c Level at Week 12 and Months 6 and 12
Hide Description HbA1c levels were recorded at Screening, Baseline (Day 1), Day 28, Week 8, Week 12, Months 4 to 12 and Month 24. Data has been presented for HbA1c levels at Week 12 and Months 6 and 12.
Time Frame Week 12 and Months 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Least Squares Mean (Standard Error)
Unit of Measure: Percentage
HbA1c levels at Month 12 6.83  (0.146) 7.02  (0.108)
HbA1c levels at Month 6 6.60  (0.138) 6.77  (0.100)
HbA1c levels at Week 12 6.45  (0.124) 6.54  (0.094)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments HbA1c levels, Placebo Vs Otelixizumab at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.289
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
-0.16 to 0.52
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments HbA1c levels, Placebo Vs Otelixizumab at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.538
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.15 to 0.49
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments HbA1c levels, Placebo Vs Otelixizumab at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.538
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.19 to 0.36
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12
Hide Description Hypoglycemic events reported by participants were classified as defined by the American Diabetes Association (ADA) Workgroup on Hypoglycemia as follows: Severe hypoglycemia: an event requiring assistance of another person to actively administer carbohydrate, glucagon/other resuscitative actions, documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration(PGC)<=70 mg/dL, asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured PGC<=70 mg/dL,probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia are not accompanied by a plasma glucose determination, but were presumably caused by a PGC<=70 mg/dL and relative hypoglycemia: an event during which the person with diabetes reports any of the typical symptoms of hypoglycemia, and interprets the symptoms as indicative of hypoglycemia, but with a measured PGC>70 mg/dL.
Time Frame Upto Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Measure Type: Number
Unit of Measure: Hypoglycemic events
Severe hypoglycemia upto Month 12 2 5
Documented symptomatic hypoglycemia upto Month 12 3092 6322
Asymptomatic hypoglycemia upto Month 12 4718 9962
Probable symptomatic hypoglycemia upto Month 12 84 93
Relative hypoglycemia upto Month 12 85 211
6.Secondary Outcome
Title Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12
Hide Description Hypoglycemic events reported by participants were classified as defined by the ADA Workgroup on Hypoglycemia as Severe hypoglycemia: an event requiring assistance of another person to actively administer carbohydrate, glucagon/other resuscitative actions, documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration (PGC)<=70 mg/dL, asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured PGC<=70 mg/dL,probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia are not accompanied by a plasma glucose determination, but were presumably caused by a PGC<=70 mg/dL and relative hypoglycemia: an event during which the person with diabetes reports any of the typical symptoms of hypoglycemia, and interprets the symptoms as indicative of hypoglycemia, but with a measured PGC>70 mg/dL. Only categories with values are presented.
Time Frame Upto Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Data has been presented for number of participants with their percentages with hypoglycemic events defined by hypoglycemic event categories from Baseline upto month 12.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Measure Type: Count of Participants
Unit of Measure: Participants
Severe hypoglycemia upto Month 12
2
   2.2%
4
   2.2%
Documented symptomatic hypoglycemia upto Month 12
78
  85.7%
163
  90.1%
Asymptomatic hypoglycemia upto Month 12
10
  11.0%
13
   7.2%
7.Secondary Outcome
Title Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.
Hide Description The event frequency of glucose measurements that were hypoglycemic excursions were calculated per participant basis, using the number of occurrences where blood glucose was less than or equal to 70 mg/dL. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected.
Time Frame Week 12 and Months 6 and 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Mean (Standard Error)
Unit of Measure: Hypoglycemic excursions
Number of hypoglycemic excursions at Week 12 Number Analyzed 90 participants 177 participants
2.3  (0.28) 2.8  (0.27)
Number of hypoglycemic excursions at Month 6 Number Analyzed 80 participants 166 participants
3.0  (0.36) 2.9  (0.27)
Number of hypoglycemic excursions at Month 12 Number Analyzed 78 participants 161 participants
2.9  (0.41) 3.2  (0.32)
8.Secondary Outcome
Title Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.
Hide Description

The greatest hypoglycemic excursions during an interval was calculated as 70 mg/dL minus the lowest recorded glucose level in the interval. If a participant had data recorded during the interval but did not have a value below 70 mg/dL, the participants greatest hypoglycemic excursion for that interval was 0 mg/dL.

Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected.

Time Frame Week 12 and Months 6 and 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Mean (Standard Error)
Unit of Measure: milligrams per deciliter
Magnitude of excursion, Week 12 Number Analyzed 90 participants 177 participants
9.4  (0.92) 10.8  (0.90)
Magnitude of excursion, Month 6 Number Analyzed 80 participants 166 participants
11.9  (1.24) 10.6  (0.77)
Magnitude of excursion, Month 12 Number Analyzed 78 participants 161 participants
11.2  (1.20) 11.0  (0.92)
9.Secondary Outcome
Title Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12
Hide Description Percentage of hypoglycemic excursions was calculated as the total number of observations that exceed the hypoglycemic excursion boundary (i.e.<= 70 mg/dL) divided by the total number of glucose measurements recorded in a time interval for the intervals: Baseline to Week 12, post-Week 12 to Month 6, post-Month 6 to Month 12. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected. Data has been presented for number of participants with their percentages having hypoglycemic excursion.
Time Frame Week 12 and Months 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Measure Type: Count of Participants
Unit of Measure: Participants
Percentage of participants with excursion,Week 12 Number Analyzed 90 participants 177 participants
72
  80.0%
127
  71.8%
Percentage of participants with excursion,Month 6 Number Analyzed 80 participants 166 participants
57
  71.3%
121
  72.9%
Percentage of participants with excursion,Month 12 Number Analyzed 78 participants 161 participants
56
  71.8%
111
  68.9%
10.Secondary Outcome
Title Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.
Hide Description The event frequency of glucose measurements that were hyperglycemic excursions were calculated on a per participant basis using the number of occurrences where blood glucose was greater than the hyperglycemic tolerance limit. There were 3 hyperglycemic tolerance limits considered: 200 mg/dL, 130 mg/dL and 100 mg/dL. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected.
Time Frame Week 12 and Months 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Mean (Standard Error)
Unit of Measure: Hyperglycemic excursions
Threshold > 100 mg/dL at Week 12 Number Analyzed 90 participants 177 participants
34.0  (1.78) 32.9  (1.15)
Threshold > 130 mg/dL at Week 12 Number Analyzed 90 participants 177 participants
20.5  (1.72) 19.9  (1.01)
Threshold > 200 mg/dL at Week 12 Number Analyzed 90 participants 177 participants
5.7  (0.85) 5.6  (0.59)
Threshold > 100 mg/dL at Month 6 Number Analyzed 80 participants 166 participants
33.5  (1.77) 35.1  (1.41)
Threshold > 130 mg/dL at Month 6 Number Analyzed 80 participants 166 participants
20.8  (1.68) 22.7  (1.25)
Threshold > 200 mg/dL at Month 6 Number Analyzed 80 participants 166 participants
6.5  (1.07) 7.9  (0.85)
Threshold > 100 mg/dL at Month 12 Number Analyzed 78 participants 161 participants
35.6  (1.97) 33.4  (1.27)
Threshold > 130 mg/dL at Month 12 Number Analyzed 78 participants 161 participants
24.0  (1.92) 22.2  (1.05)
Threshold > 200 mg/dL at Month 12 Number Analyzed 78 participants 161 participants
8.6  (1.42) 6.9  (0.59)
11.Secondary Outcome
Title Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.
Hide Description The greatest hyperglycemic excursions during an interval was calculated as the largest recorded glucose level in the interval minus the hyperglycemic tolerance limit value (HGTLV). If a participant had data recorded during the interval but did not have a value above the HGTLV, the participants greatest hyperglycemic excursion for that interval was 0 mg/dL. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected.
Time Frame Week 12 and Months 6 and 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions (as first dose-day 1 of 0.1 mg, second dose-day 2 of 0.2 mg, third dose-day 3 of 0.3 mg, fourth, fifth, sixth, seventh and eight dose on days 4,5,6,7,8 of 0.5 mg per day) 1 infusion per day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg.
Overall Number of Participants Analyzed 91 181
Mean (Standard Error)
Unit of Measure: milligrams per deciliter
Threshold> 100 mg/dL at Week 12 Number Analyzed 90 participants 177 participants
158.3  (9.26) 158.4  (6.65)
Threshold> 130 mg/dL at Week 12 Number Analyzed 90 participants 177 participants
128.3  (9.26) 128.4  (6.65)
Threshold> 200 mg/dL at Week 12 Number Analyzed 90 participants 177 participants
65.7  (8.51) 65.7  (6.12)
Threshold> 100 mg/dL at Month 6 Number Analyzed 80 participants 166 participants
154.6  (9.34) 175.7  (8.09)
Threshold> 130 mg/dL at Month 6 Number Analyzed 80 participants 166 participants
124.8  (9.31) 145.7  (8.09)
Threshold> 200 mg/dL at Month 6 Number Analyzed 80 participants 166 participants
63.3  (8.32) 80.1  (7.75)
Threshold> 100 mg/dL at Month 12 Number Analyzed 78 participants 161 participants
176.7  (10.02) 177.5  (7.08)
Threshold> 130 mg/dL at Month 12 Number Analyzed 78 participants 161 participants
146.8  (10.00) 147.5  (7.07)
Threshold> 200 mg/dL at Month 12 Number Analyzed 78 participants 161 participants
81.8  (9.33) 82.6  (6.61)
12.Secondary Outcome
Title Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12
Hide Description Percentage of hyperglycemic excursions was calculated as the total number of observations that exceed the hyperglycemic excursion boundary (i.e. > HGTLV) divided by the total number of glucose measurements recorded in a time interval for the intervals: Baseline to Week 12, post-Week 12 to Month 6, post-Month 6 to Month 12. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected. Data for number of participants with their percentages are presented.
Time Frame Week 12 and Months 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Measure Type: Count of Participants
Unit of Measure: Participants
Threshold> 100 mg/dL at Week 12 Number Analyzed 90 participants 177 participants
90
 100.0%
177
 100.0%
Threshold> 130 mg/dL at Week 12 Number Analyzed 90 participants 177 participants
90
 100.0%
177
 100.0%
Threshold> 200 mg/dL at Week 12 Number Analyzed 90 participants 177 participants
65
  72.2%
130
  73.4%
Threshold> 100 mg/dL at Month 6 Number Analyzed 80 participants 166 participants
80
 100.0%
166
 100.0%
Threshold> 130 mg/dL at Month 6 Number Analyzed 80 participants 166 participants
79
  98.8%
166
 100.0%
Threshold> 200 mg/dL at Month 6 Number Analyzed 80 participants 166 participants
57
  71.3%
139
  83.7%
Threshold> 100 mg/dL at Month 12 Number Analyzed 78 participants 161 participants
78
 100.0%
161
 100.0%
Threshold> 130 mg/dL at Month 12 Number Analyzed 78 participants 161 participants
77
  98.7%
160
  99.4%
Threshold> 200 mg/dL at Month 12 Number Analyzed 78 participants 161 participants
60
  76.9%
131
  81.4%
13.Secondary Outcome
Title Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.
Hide Description Average daily risk range is a measure for evaluation of blood glucose variability that was designed to be equally sensitive to hypoglycemia and hyperglycemia. The ADRR was assessed over 30-day periods prior to Baseline and at key visits Week 12 and Months 6 and 12. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Week 12 and Months 6 and 12.
Time Frame Baseline (Day 1) and Week 12, Months 6 and 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Least Squares Mean (Standard Error)
Unit of Measure: Ratio
ADRR at Week 12 -0.41  (0.826) 0.71  (0.599)
ADRR at Month 6 2.03  (1.133) 2.86  (0.801)
ADRR at Month 12 3.29  (1.038) 4.22  (0.732)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments ADRR, Placebo Vs Otelixizumab at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.540
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
-0.88 to 3.11
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments ADRR, Placebo Vs Otelixizumab at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.546
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
-1.89 to 3.56
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments ADRR, Placebo Vs Otelixizumab at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.462
Comments [Not Specified]
Method Mixed effects repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
-1.56 to 3.42
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12
Hide Description O’Brien mean rank analyses was performed on a two-part composite of the baseline-adjusted HbA1c level and the baseline-adjusted mean total daily insulin use per kg body weight in the otelixizumab group compared with the placebo group at Months 6, 12. For the O’Brien mean rank analysis at a particular time point, adjusted HbA1c values (for both treatment groups together) was ranked from smallest to largest, and adjusted mean daily insulin use values were ranked from smallest to largest. For each participant, the HbA1c and insulin use ranks were added together, producing a composite rank. A treatment comparison test was then performed on the composite ranks.
Time Frame Month 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Mean (Standard Deviation)
Unit of Measure: Composite rank score
Composite rank summary, Month 6 Number Analyzed 73 participants 156 participants
238  (123.3) 247  (113.7)
Composite rank summary, Month 12 Number Analyzed 76 participants 158 participants
245  (120.0) 244  (115.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Composite Rank Summary for HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.957
Comments [Not Specified]
Method Hochberg-adjusted
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Composite Rank Summary for HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.957
Comments [Not Specified]
Method Hochberg-adjusted
Comments [Not Specified]
15.Secondary Outcome
Title Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12
Hide Description O’Brien analyses will be performed on a three-part composite of HbA1c level, C-peptide AUC, and mean daily Insulin use in the otelixizumab group compared with the placebo group at Months 6 and12. For the O’Brien mean rank analysis at a particular time point, HbA1c and insulin use will be ranked from smallest to largest, and C-peptide AUC will be ranked from largest to smallest. For each participant, the C-Peptide AUC, ranks for HbA1c and insulin use were added together, producing a composite rank. A treatment comparison test was then performed on the composite ranks.
Time Frame Month 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Mean (Standard Deviation)
Unit of Measure: Composite rank score
Month 6 Number Analyzed 72 participants 151 participants
365  (83.8) 373  (105.6)
Month 12 Number Analyzed 74 participants 151 participants
360  (85.1) 366  (95.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.653
Comments [Not Specified]
Method Hochberg-adjusted
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.653
Comments [Not Specified]
Method Hochberg-adjusted
Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline in Level of Cytokines Interleukin (IL-6), IL-10 and Tumor Necrosis Factor-alpha (TNF-a) at Day 1, Day 4, Day 8
Hide Description Levels of cytokine (TNFα, IL-6, IL-10) were measured at Baseline and at 2 hours after end of infusion (EOI) on Day 1, Day 4, Day 8 . Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Day 1, Day 4 and Day 8.
Time Frame Day 1, Day 4, Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Mean (Standard Error)
Unit of Measure: picograms per milliliter
IL-6 levels, Day 1, 2 hours after EOI Number Analyzed 24 participants 50 participants
0.76  (0.680) 2.78  (0.544)
IL-6 levels, Day 4, 2 hours after EOI Number Analyzed 24 participants 44 participants
-0.13  (0.251) 3.01  (1.107)
IL-6 levels, Day 8, 2 hours after EOI Number Analyzed 23 participants 50 participants
0.45  (0.448) 14.59  (5.266)
IL-10 levels, Day 1, 2 hours after EOI Number Analyzed 23 participants 50 participants
0.15  (0.342) 4.61  (1.770)
IL-10 levels, Day 4, 2 hours after EOI Number Analyzed 23 participants 44 participants
0.55  (0.629) 1.35  (0.575)
IL-10 levels, Day 8, 2 hours after EOI Number Analyzed 22 participants 49 participants
1.84  (1.019) 25.57  (7.196)
TNF-a levels, Day 1, 2 hours after EOI Number Analyzed 24 participants 50 participants
-0.126  (0.0719) 2.320  (0.3996)
TNF-a levels, Day 4, 2 hours after EOI Number Analyzed 24 participants 44 participants
0.111  (0.2381) 1.509  (0.5740)
TNF-a levels, Day 8, 2 hours after EOI Number Analyzed 23 participants 50 participants
0.135  (0.2649) 3.614  (0.8920)
17.Secondary Outcome
Title Percent Change From Baseline in Circulating Peripheral Lymphocytes CD4+CD25+FoxP3+ T Cells and CD4+CD25hiFoxP3+ T Cells in Type 1 Diabetes Mellitus (TIDM) up to Month 12
Hide Description Blood samples were drawn for lymphocyte subset evaluations at Baseline and at 2hours after EOI on Day 4, pre-dose and after E0I on Day 8, Day 14, Day 21, Day 28, Week 6, Week 8, Week 10, Week 12, Month 6 and Month 12. Percentages of relevant lymphocyte subsets were determined by flow cytometry. The lymphocyte subsets assessed included CD8+CD25+ T lymphocytes, as well as the subsets of lymphocytes of these type that were positive for FoxP3, a protein that was expressed at high levels in the cytoplasm of regulatory T cells. CD4+CD25hiFoxP3+ T lymphocytes, a cell type was of interest because it played a regulatory role in T1DM. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.
Time Frame Baseline (pre-dose on Day 1) and up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Median (Full Range)
Unit of Measure: Percent change
CD4+CD25+FoxP3+ T, Day 4, 2 hours after EOI Number Analyzed 28 participants 56 participants
118.8
(32.1 to 366.9)
53.4
(3.4 to 235.9)
CD4+CD25+FoxP3+ T, Day 8 pre-dose Number Analyzed 27 participants 57 participants
94.4
(25.9 to 199.9)
49.7
(9.4 to 148.5)
CD4+CD25+FoxP3+ T, Day 8, 2 hours after EOI Number Analyzed 70 participants 146 participants
113.2
(28.8 to 2127.6)
40.1
(2.1 to 3737.0)
CD4+CD25+FoxP3+ T, Day 14 Number Analyzed 72 participants 153 participants
114.5
(26.5 to 2384.4)
101.3
(15.5 to 10906.4)
CD4+CD25+FoxP3+ T, Day 21 Number Analyzed 74 participants 147 participants
114.6
(34.8 to 489.8)
101.9
(0.0 to 44228.1)
CD4+CD25+FoxP3+ T, Day 28 Number Analyzed 75 participants 151 participants
95.1
(7.0 to 1612.7)
101.7
(2.1 to 6363.7)
CD4+CD25+FoxP3+ T, Week 6 Number Analyzed 72 participants 148 participants
104.1
(0.0 to 514.2)
106.6
(0.0 to 7010.9)
CD4+CD25+FoxP3+ T, Week 8 Number Analyzed 75 participants 156 participants
110.1
(29.1 to 1602.3)
107.1
(4.7 to 15806.4)
CD4+CD25+FoxP3+ T, Week 10 Number Analyzed 75 participants 145 participants
109.9
(8.6 to 1820.9)
102.7
(7.4 to 9943.6)
CD4+CD25+FoxP3+ T, Week 12 Number Analyzed 75 participants 150 participants
102.5
(9.8 to 1018.7)
85.5
(2.9 to 9911.7)
CD4+CD25+FoxP3+ T, Month 6 Number Analyzed 72 participants 146 participants
137.9
(19.5 to 1409.6)
133.3
(19.8 to 10357.4)
CD4+CD25+FoxP3+ T, Month 12 Number Analyzed 70 participants 149 participants
122.0
(9.5 to 628.7)
106.9
(0.4 to 31690.3)
CD4+CD25hiFoxP3+ T Cells, Day 4, 2 hours after EOI Number Analyzed 28 participants 56 participants
151.9
(12.6 to 400.8)
60.8
(1.5 to 364.5)
CD4+CD25hiFoxP3+ T Cells, Day 8 pre-dose Number Analyzed 27 participants 57 participants
93.8
(13.6 to 521.7)
43.5
(3.6 to 675.0)
CD4+CD25hiFoxP3+ T Cells, Day 8, 2 hours after EOI Number Analyzed 69 participants 146 participants
110.7
(18.6 to 3577.8)
35.9
(0.0 to 321279)
CD4+CD25hiFoxP3+ T Cells, Day 14 Number Analyzed 71 participants 153 participants
118.4
(8.8 to 1502.5)
109.7
(5.8 to 1364664)
CD4+CD25hiFoxP3+ T Cells, Day 21 Number Analyzed 74 participants 147 participants
110.0
(9.7 to 1720.2)
98.8
(0.0 to 1479653)
CD4+CD25hiFoxP3+ T Cells, Day 28 Number Analyzed 74 participants 151 participants
101.1
(2.1 to 949.9)
108.7
(0.0 to 62190.9)
CD4+CD25hiFoxP3+ T Cells, Week 6 Number Analyzed 72 participants 148 participants
106.9
(0.0 to 2508.7)
110.7
(0.0 to 9573.5)
CD4+CD25hiFoxP3+ T Cells, Week 8 Number Analyzed 74 participants 156 participants
131.7
(14.1 to 843.2)
120.3
(0.5 to 175040)
CD4+CD25hiFoxP3+ T Cells, Week 10 Number Analyzed 74 participants 145 participants
97.7
(1.5 to 2356.8)
107.0
(0.0 to 128591)
CD4+CD25hiFoxP3+ T Cells, Week 12 Number Analyzed 74 participants 150 participants
113.6
(1.9 to 1310.2)
90.9
(0.1 to 1045228)
CD4+CD25hiFoxP3+ T Cells, Month 6 Number Analyzed 71 participants 146 participants
150.9
(6.1 to 25639.5)
153.2
(5.5 to 1544544)
CD4+CD25hiFoxP3+ T Cells, Month 12 Number Analyzed 69 participants 149 participants
166.4
(5.1 to 1748.9)
160.6
(0.0 to 78843.4)
18.Secondary Outcome
Title Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8
Hide Description The amount of cell-bound otelixizumab was determined by flow cytometry. The extent of T cell receptor alpha beta (TCRαβ) expression was determined using an antibody that bound to TCRαβ but did not compete with otelixizumab for binding sites at the expected range of concentrations. The MESF of the anti-TCRαβ antibody was used to quantify the number of CD3/TCR complexes present on T cells. Free otelixizumab binding sites (sites not occupied by otelixizumab) were detected by staining with biotinylated otelixizumab. The MESF of bound biotinylated otelixizumab was directly proportional to the availability of free otelixizumab binding sites. MESF of bound antibody on CD4+ T cells was a direct measurement of cell-bound otelixizumab on CD4+ T cells. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Day 1, Day 4 and Day 8.
Time Frame Baseline (pre-dose on Day 1), Day 4 and Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Mean (Standard Error)
Unit of Measure: Percent change
CD4+ T cells, Day 1, 2 hours after EOI Number Analyzed 20 participants 57 participants
125.1  (18.00) 914.8  (269.18)
CD4+ T cells, Day 4, 2 hours after EOI Number Analyzed 23 participants 54 participants
174.3  (41.95) 2719.8  (369.41)
CD4+ T cells, Day 8, pre-dose Number Analyzed 26 participants 54 participants
151.5  (39.49) 471.5  (98.53)
CD4+ T cells, Day 8, 2 hours after EOI Number Analyzed 26 participants 57 participants
167.9  (47.67) 1387.5  (274.21)
19.Secondary Outcome
Title Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8
Hide Description The extent of saturation of CD3/TCR receptors on CD4+ and CD8+ lymphocytes was determined by flow cytometry. The extent of TCRαβ expression was determined using an antibody that bound to TCRαβ but did not compete with otelixizumab for binding sites at the expected range of concentrations. The MESF of the anti-TCRαβ antibody was used to quantify the number of CD3/TCR complexes present on T cells. The MESF of bound biotinylated otelixizumab was directly proportional to the availability of free otelixizumab binding sites. MESF of free CD3 sites on CD4+ T cells and CD8+ T cells was direct measurement of saturation of the CD3/TCR complex on CD4+ T cells and CD8+ T cells. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Day 1, Day 4 and Day 8.
Time Frame Baseline (Pre-dose Day 1), Day 4, Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions (as first dose-day 1 of 0.1 mg, second dose-day 2 of 0.2 mg, third dose-day 3 of 0.3 mg, fourth, fifth, sixth, seventh and eight dose on days 4,5,6,7,8 of 0.5 mg per day) 1 infusion per day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg.
Overall Number of Participants Analyzed 91 181
Mean (Standard Error)
Unit of Measure: Percent change
CD4+ T cells, Day 1, 2 hours after EOI Number Analyzed 20 participants 57 participants
93.4  (2.40) 90.9  (3.82)
CD4+ T cells, Day 4, 2 hours after EOI Number Analyzed 23 participants 54 participants
109.7  (11.91) 50.2  (4.90)
CD4+ T cells, Day 8, pre-dose Number Analyzed 26 participants 54 participants
97.7  (10.66) 59.0  (5.31)
CD4+ T cells, Day 8, 2 hours after EOI Number Analyzed 26 participants 56 participants
98.0  (13.03) 21.7  (3.33)
CD8+ T cells, Day 1, 2 hours after EOI Number Analyzed 20 participants 57 participants
92.4  (2.38) 91.4  (3.82)
CD8+ T cells, Day 4, 2 hours after EOI Number Analyzed 23 participants 54 participants
116.7  (14.53) 51.6  (5.23)
CD8+ T cells, Day 8, pre-dose Number Analyzed 26 participants 54 participants
97.4  (11.84) 60.8  (6.11)
CD8+ T cells, Day 8, 2 hours after EOI Number Analyzed 26 participants 56 participants
98.2  (14.63) 23.0  (3.72)
20.Secondary Outcome
Title Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8
Hide Description The extent of modulation of CD3/TCR receptors on CD4+ and CD8+ lymphocytes was determined by flow cytometry. The extent of TCRαβ expression was determined using an antibody that bound to TCRαβ but did not compete with otelixizumab for binding sites at the expected range of concentrations. The MESF of the anti-TCRαβ antibody was used to quantify the number of CD3/TCR complexes present on T cells. The MESF of bound biotinylated otelixizumab was directly proportional to the availability of free otelixizumab binding sites.CD3/TCR complexes on CD4+ and CD8+ T cells were detected with a non-competing antibody. Changes in the MESF of TCR expression was a direct measurement of TCR modulation. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Day 1, Day 4 and Day 8.
Time Frame Baseline (Pre-dose Day 1), Day 4, Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed 91 181
Mean (Standard Error)
Unit of Measure: Percent change
CD4+ T cells, Day 1, 2 hours after EOI Number Analyzed 20 participants 57 participants
94.2  (2.95) 91.1  (2.90)
CD4+ T cells, Day 4, 2 hours after EOI Number Analyzed 23 participants 54 participants
103.8  (8.93) 70.8  (3.89)
CD4+ T cells, Day 8, pre-dose Number Analyzed 26 participants 54 participants
101.4  (6.09) 61.0  (2.65)
CD4+ T cells, Day 8, 2 hours after EOI Number Analyzed 26 participants 57 participants
103.4  (5.87) 32.2  (2.52)
CD8+ T cells, Day 1, 2 hours after EOI Number Analyzed 20 participants 57 participants
95.2  (2.72) 93.7  (3.06)
CD8+ T cells, Day 4, 2 hours after EOI Number Analyzed 23 participants 54 participants
111.1  (10.56) 77.1  (4.33)
CD8+ T cells, Day 8, pre-dose Number Analyzed 26 participants 54 participants
101.8  (6.19) 62.3  (2.68)
CD8+ T cells, Day 8, 2 hours after EOI Number Analyzed 26 participants 57 participants
103.0  (6.05) 36.2  (2.52)
Time Frame Upto Month 24
Adverse Event Reporting Description Safety was used for analysis which comprised of all participants who received any part of at least 1 infusion of study drug.
 
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose. Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
All-Cause Mortality
Placebo Otelixizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   0/91 (0.00%)      0/181 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Otelixizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/91 (6.59%)      15/181 (8.29%)    
Gastrointestinal disorders     
Anal fistula  1  0/91 (0.00%)  1/181 (0.55%) 
Gastritis erosive  1  0/91 (0.00%)  1/181 (0.55%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/91 (1.10%)  0/181 (0.00%) 
Immune system disorders     
Cytokine release syndrome  1  0/91 (0.00%)  3/181 (1.66%) 
Infections and infestations     
Anal abscess  1  0/91 (0.00%)  1/181 (0.55%) 
Appendicitis  1  1/91 (1.10%)  0/181 (0.00%) 
Gastroenteritis viral  1  1/91 (1.10%)  0/181 (0.00%) 
Septic embolus  1  0/91 (0.00%)  1/181 (0.55%) 
Tonsillitis  1  1/91 (1.10%)  0/181 (0.00%) 
Viral upper respiratory tract infection  1  1/91 (1.10%)  0/181 (0.00%) 
Injury, poisoning and procedural complications     
Alcohol poisoning  1  0/91 (0.00%)  1/181 (0.55%) 
Ligament rupture  1  0/91 (0.00%)  1/181 (0.55%) 
Road traffic accident  1  0/91 (0.00%)  1/181 (0.55%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  0/91 (0.00%)  1/181 (0.55%) 
Hypoglycaemic seizure  1  0/91 (0.00%)  1/181 (0.55%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  0/91 (0.00%)  1/181 (0.55%) 
Nervous system disorders     
Neurological symptom  1  1/91 (1.10%)  0/181 (0.00%) 
Paraesthesia  1  0/91 (0.00%)  1/181 (0.55%) 
Pregnancy, puerperium and perinatal conditions     
Abortion missed  1  0/91 (0.00%)  1/181 (0.55%) 
Psychiatric disorders     
Alcohol abuse  1  0/91 (0.00%)  1/181 (0.55%) 
Major depression  1  1/91 (1.10%)  0/181 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Otelixizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   81/91 (89.01%)      173/181 (95.58%)    
Blood and lymphatic system disorders     
Lymphadenopathy  1  13/91 (14.29%)  20 18/181 (9.94%)  37
Gastrointestinal disorders     
Nausea  1  20/91 (21.98%)  32 60/181 (33.15%)  91
Vomiting  1  13/91 (14.29%)  15 35/181 (19.34%)  40
Diarrhoea  1  8/91 (8.79%)  9 13/181 (7.18%)  19
General disorders     
Fatigue  1  20/91 (21.98%)  32 42/181 (23.20%)  58
Pyrexia  1  10/91 (10.99%)  10 34/181 (18.78%)  45
Chills  1  6/91 (6.59%)  9 24/181 (13.26%)  32
Malaise  1  2/91 (2.20%)  2 10/181 (5.52%)  13
Infections and infestations     
Nasopharyngitis  1  29/91 (31.87%)  42 48/181 (26.52%)  83
Upper respiratory tract infection  1  10/91 (10.99%)  15 22/181 (12.15%)  29
Sinusitis  1  4/91 (4.40%)  4 12/181 (6.63%)  17
Pharyngitis  1  9/91 (9.89%)  13 4/181 (2.21%)  4
Viral infection  1  6/91 (6.59%)  9 3/181 (1.66%)  4
Investigations     
Blood creatine phosphokinase increased  1  6/91 (6.59%)  6 8/181 (4.42%)  8
Metabolism and nutrition disorders     
Hypoglycaemia  1  8/91 (8.79%)  16 22/181 (12.15%)  83
Musculoskeletal and connective tissue disorders     
Myalgia  1  14/91 (15.38%)  27 21/181 (11.60%)  32
Arthralgia  1  2/91 (2.20%)  4 20/181 (11.05%)  23
Back pain  1  5/91 (5.49%)  5 13/181 (7.18%)  16
Pain in extremity  1  5/91 (5.49%)  5 9/181 (4.97%)  11
Nervous system disorders     
Headache  1  45/91 (49.45%)  117 155/181 (85.64%)  441
Dizziness  1  12/91 (13.19%)  20 18/181 (9.94%)  23
Psychiatric disorders     
Insomnia  1  5/91 (5.49%)  5 5/181 (2.76%)  6
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  24/91 (26.37%)  35 25/181 (13.81%)  35
Cough  1  10/91 (10.99%)  11 19/181 (10.50%)  24
Nasal congestion  1  7/91 (7.69%)  9 8/181 (4.42%)  13
Rhinorrhoea  1  2/91 (2.20%)  2 10/181 (5.52%)  11
Sinus congestion  1  5/91 (5.49%)  5 5/181 (2.76%)  7
Skin and subcutaneous tissue disorders     
Rash macular  1  3/91 (3.30%)  3 10/181 (5.52%)  17
Rash papular  1  0/91 (0.00%)  0 12/181 (6.63%)  15
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
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.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00678886     History of Changes
Obsolete Identifiers: NCT00893022
Other Study ID Numbers: 115495
TRX4006 ( Other Identifier: Tolerx )
First Submitted: May 13, 2008
First Posted: May 16, 2008
Results First Submitted: July 19, 2017
Results First Posted: October 3, 2017
Last Update Posted: October 3, 2017