Non-inferiority Study to Compare the Efficacy and Safety of Mylan's Insulin Glargine With Lantus® in Type 1 Diabetes Mellitus Patients (INSTRIDE 1)

• Sponsor: Mylan Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02227862
• Collaborator: Mylan GmbH (Industry)
• Enrollment: 558
• Locations: 162
• Arms: 2
• Actual Duration (Months): 25
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To test whether Mylan's insulin glargine once daily is non-inferior to Lantus® once daily (based on change in HbA1c from baseline to 24 weeks) when administered in combination with mealtime insulin lispro.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Drug: Mylan's insulin glargine; Drug: Lantus®	Phase 3

Detailed Description

This trial is a multicenter, open-label, randomized, parallel-group trial in patients with Type 1 Diabetes Mellitus (T1DM) comparing the efficacy and safety of Mylan's insulin glargine with that of Lantus®.

Study Design

• Study Type: Interventional
• Actual Enrollment: 558 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Randomized, Multi-Center, Parallel-Group Clinical Trial Comparing the Efficacy and Safety of Mylan's Insulin Glargine With Lantus® in Type 1 Diabetes Mellitus Patients
• Actual Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mylan's Insulin Glargine Receive Mylan's Insulin Glargine plus insulin lispro.	Drug: Mylan's insulin glargine; All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Active Comparator: Lantus® Receive Lantus® plus insulin lispro	Drug: Lantus®; All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c From Baseline to 24 Weeks [24 weeks]

Secondary Outcome Measures

1. Summary of Actual and Change From Baseline in HbA1c [24 and 52 weeks]

2. Change From Baseline in FPG Over Time [24 and 52 weeks]

3. Change From Baseline in 8-point SMBG Profile Over Time [24 and 52 weeks]

4. Change in Total Daily Insulin Dose Per Unit Body Weight From Baseline Over Time [24 and 52 weeks]

5. Rate of Hypoglycemic Events Per 30 Days Over Time [24 and 52 weeks]

6. Hypoglycemia Occurrence [52 weeks]

7. Occurrence of Local and Systematic Reactions [52 weeks]

8. Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time [24 and 52 weeks]

9. Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time [24 and 52 weeks]

10. Change in Cross-reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time [24 and 52 weeks]

11. Change in Cross-reactive Insulin Antibody Percent Binding for Lantus Assay Over Time [24 and 52 weeks]

12. Proportion of Patients With HbA1c < 7% [24 and 52 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with an established diagnosis of T1DM per ADA 2014 criteria

• Body mass index (BMI) of 18.5 to 35 kg/m2 at screening (both values inclusive).

• Glycosylated hemoglobin (HbA1c) ≤9.5% at screening.

• Hemoglobin ≥9.0 g/dL at screening.

Exclusion Criteria:

• History of hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analogue preparations used in the trial, OR history of significant allergic drug reactions.

• History of use of animal insulin within the last 3 years or use of biosimilar insulin glargine at any time prior.

• History of use of a regular immunomodulator therapy in the 1 year prior to screening.

• History of ≥2 episodes of severe hypoglycemia within the 6 months before screening or history of hypoglycemia unawareness (a sample questionnaire is provided in Appendix I), as judged by the investigator.

• History of ≥1 episodes of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months prior to screening.

• Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg) or hepatitis C (HCVAb) antibodies at screening.

• History of drug or alcohol dependence or abuse during the 1 year prior to screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mylan Investigational Site	Bell Gardens	California	United States	90201
2	Mylan Investigational Site	Fresno	California	United States	93720
3	Mylan Investigational Site	Greenbrae	California	United States	93720
4	Mylan Investigational Site	La Jolla	California	United States	92037
5	Mylan Investigational Site	La Mesa	California	United States	91942
6	Mylan Investigational Site	Long Beach	California	United States	90807
7	Mylan Investigational Site	Los Gatos	California	United States	95032
8	Mylan Investigational Site	Mission Hills	California	United States	91345
9	Mylan Investigational Site	National City	California	United States	91950
10	Mylan Investigational Site	Northridge	California	United States	91324
11	Mylan Investigational Site	Tustin	California	United States	92780
12	Mylan Investigational Site	Walnut Creek	California	United States	94598
13	Mylan Investigational Site	Bradenton	Florida	United States	34208
14	Mylan Investigational Site	Cooper City	Florida	United States	33024
15	Mylan Investigational Site	Hialeah	Florida	United States	33012
16	Mylan Investigational Site	Hollywood	Florida	United States	33021
17	Mylan Investigational Site	Miami	Florida	United States	33142
18	Mylan Investigational Site	Miami	Florida	United States	33156
19	Mylan Investigational Site	New Port Richey	Florida	United States	34652
20	Mylan Investigational Site	Palm Harbor	Florida	United States	34684
21	Mylan Investigational Site	West Palm Beach	Florida	United States	33401
22	Mylan Investigational Site	Atlanta	Georgia	United States	30318
23	Mylan Investigational Site	Columbus	Georgia	United States	31904
24	Mylan Investigational Site	Honolulu	Hawaii	United States	96814
25	Mylan Investigational Site	Idaho Falls	Idaho	United States	83404
26	Mylan Investigational Site	Crystal Lake	Illinois	United States	60012
27	Mylan Investigational Site	LaGrange	Illinois	United States	60525
28	Mylan Investigational Site	Springfield	Illinois	United States	62704
29	Mylan Investigational Site	Anderson	Indiana	United States	46011
30	Mylan Investigational Site	Muncie	Indiana	United States	47304
31	Mylan Investigational Site	Council Bluffs	Iowa	United States	51501
32	Mylan Investigational Site	Des Moines	Iowa	United States	50314
33	Mylan Investigational Site	Overland Park	Kansas	United States	66210
34	Mylan Investigational Site	Topeka	Kansas	United States	66606
35	Mylan Investigational Site	Lexington	Kentucky	United States	40503
36	Mylan Investigational Site	Billings	Montana	United States	59101
37	Mylan Investigational Site	Omaha	Nebraska	United States	68114
38	Mylan Investigational Site	Omaha	Nebraska	United States	68131
39	Mylan Investigational Site	Las Vegas	Nevada	United States	89128
40	Mylan Investigational Site	Albany	New York	United States	12206
41	Mylan Investigational Site	Mineola	New York	United States	11501
42	Mylan Investigational Site	Staten Island	New York	United States	10301
43	Mylan Investigational Site	Syracuse	New York	United States	13210
44	Mylan Investigational Site	Asheville	North Carolina	United States	28803
45	Mylan Investigational Site	Burlington	North Carolina	United States	27215
46	Mylan Investigational Site	Greensboro	North Carolina	United States	27408
47	Mylan Investigational Site	Greenville	North Carolina	United States	27834
48	Mylan Investigational Site	Hickory	North Carolina	United States	28601
49	Mylan Investigational Site	Morehead City	North Carolina	United States	28557
50	Mylan Investigational Site	Wilmington	North Carolina	United States	28401
51	Mylan Investigational Site	Cincinnati	Ohio	United States	45236
52	Mylan Investigational Site	Mentor	Ohio	United States	44060
53	Mylan Investigational Site	Bend	Oregon	United States	97701
54	Mylan Investigational Site	Corvallis	Oregon	United States	97330
55	Mylan Investigational Site	Chattanooga	Tennessee	United States	37411
56	Mylan Investigational Site	Memphis	Tennessee	United States	38119
57	Mylan Investigational Site	Austin	Texas	United States	78731
58	Mylan Investigational Site	Dallas	Texas	United States	75231
59	Mylan Investigational Site	El Paso	Texas	United States	79925
60	Mylan Investigational Site	Round Rock	Texas	United States	78681
61	Texas Diabetes & Endocrinology	Round Rock	Texas	United States	78681
62	Mylan Investigational Site	San Antonio	Texas	United States	78258
63	Mylan Investigational Site	Ogden	Utah	United States	84405
64	Mylan Investigational Site	Salt Lake City	Utah	United States	84102
65	Mylan Investigational Site	Salt Lake City	Utah	United States	84109
66	Mylan Investigational Site	Salt Lake City	Utah	United States	84121
67	Mylan Investigational Site	South Jordan	Utah	United States	84095
68	Mylan Investigational Site	Chesapeake	Virginia	United States	23321
69	Mylan Investigational Site	Manassas	Virginia	United States	20110
70	Mylan Investigational Site	Renton	Washington	United States	98057
71	Mylan Investigational Site	Tacoma	Washington	United States	98405
72	Mylan Investigational Site	Vancouver	Washington	United States	98664
73	Mylan Investigational Site	Red Deer	Alberta	Canada	T4N 6V7
74	Mylan Investigational Site	Vancouver	British Columbia	Canada	V6E IM7
75	Mylan Investigational Site	Winnipeg	Manitoba	Canada	R3E 3P4
76	Mylan Investigational Site	Laval	Quebec	Canada	H7T 2P5
77	Mylan Investigational Site	Mirabel	Quebec	Canada	J7J 2K8
78	Mylan Investigational Site	Montreal	Quebec	Canada	H3A 1A1
79	Mylan Investigational Site	Brno		Czechia	625 00
80	Mylan Investigational Site	Brno		Czechia	656 91
81	Mylan Investigational Site	Broumov		Czechia	55016
82	Mylan Investigational Site	Bruntal		Czechia	792 01
83	Mylan Investigational Site	Ceske Budejovice		Czechia	370 00
84	Mylan Investigational Site	Olomouc		Czechia	77900
85	Mylan Investigational Site	Pardubice		Czechia	530 02
86	Mylan Investigational Site	Praha 10		Czechia	100 00
87	Mylan Investigational Site	Praha 10		Czechia	100 34
88	Mylan Investigational Site	Parnu		Estonia	80018
89	Mylan Investigational Site	Tallinn		Estonia	13419
90	Mylan Investigational Site	Tartu		Estonia	51014
91	Mylan Investigational Site	Hohenmölsen	Anhalt	Germany	06679
92	Mylan Investigational Site	Wangen im Allgau	Baden Wuerttemberg	Germany	88239
93	Mylan Investigational Site	Aschaffenburg	Bayern	Germany	63739
94	Mylan Investigational Site	Schweinfurt	Bayern	Germany	97421
95	Mylan Investigational Site	Frankfurt	Hessen	Germany	60596
96	Mylan Investigational Site	Muenster	Nordrhein Westfalen	Germany	48145
97	Mylan Investigational Site	Sankt Ingbert	Saarland	Germany	66386
98	Mylan Investigational Site	Dresden	Sachsen	Germany	01307
99	Mylan Investigational Site	Hamburg		Germany	21073
100	Mylan Investigational Site	Hamburg		Germany	22603
101	Mylan Investigational Site	Baja		Hungary	6500
102	Mylan Investigational Site	Budapest		Hungary	1033
103	Mylan Investigational Site	Budapest		Hungary	1083
104	Mylan Investigational Site	Budapest		Hungary	1088
105	Mylan Investigational Site	Eger		Hungary	3300
106	Mylan Investigational Site	Gyula		Hungary	5700
107	Mylan Investigational Site	Letavertes		Hungary	4281
108	Mylan Investigational Site	Mako		Hungary	H-6900
109	Mylan Investigational Site	Miskolc		Hungary	3530
110	Mylan Investigational Site	Szeged		Hungary	6722
111	Mylan Investigational Site	Kuldiga		Latvia	LC-3301
112	Mylan Investigational Site	Limbazi		Latvia	4001
113	Mylan Investigational Site	Ogre		Latvia	LV-5001
114	Mylan Investigational Site	Riga		Latvia	LV-1011
115	Mylan Investigational Site	Riga		Latvia	LV-1050
116	Mylan Investigational Site	Riga		Latvia	LV1002
117	Mylan Investigational Site	Sigulda		Latvia	LV-3200
118	Mylan Investigational Site	Talsi		Latvia	LV-3200
119	Mylan Investigational Site	Bacau		Romania	600164
120	Mylan Investigational Site	Baia Mare		Romania	430222
121	Mylan Investigational Site	Bucuresti		Romania	010825
122	Mylan Investigational Site	Bucuresti		Romania	061072
123	Mylan Investigational Site	Buzau		Romania	120203
124	Mylan Investigational Site	Cluj Napoca		Romania	400349
125	Mylan Investigational Site	Galati		Romania	800578
126	Mylan Investigational Site	Iasi		Romania	700503
127	Mylan Investigational Site	Oradea		Romania	410169
128	Mylan Investigational Site	Oradea		Romania	410469
129	Mylan Investigational Site	Timisoara		Romania	300456
130	Mylan Investigational Site	Banska Bystrica		Slovakia	97517
131	Mylan Investigational Site	Bardejov		Slovakia	08501
132	Mylan Investigational Site	Bratislava		Slovakia	82106
133	Mylan Investigational Site	Bratislava		Slovakia	83331
134	Mylan Investigational Site	Bratislava		Slovakia	85101
135	Mylan Investigational Site	Dolny Kubin		Slovakia	02601
136	Mylan Investigational Site	Kosice		Slovakia	04011
137	Mylan Investigational Site	Levice		Slovakia	93401
138	Mylan Investigational Site	Lubochna		Slovakia	03491
139	Mylan Investigational Site	Nove Mesto nad Vahom		Slovakia	91501
140	Mylan Investigational Site	Nove Zamky		Slovakia	94002
141	Mylan Investigational Site	Presov		Slovakia	08001
142	Mylan Investigational Site	Prievidza		Slovakia	97101
143	Mylan Investigational Site	Pruske		Slovakia	01852
144	Mylan Investigational Site	Rimavska Sobota		Slovakia	97901
145	Mylan Investigational Site	Sabinov		Slovakia	08301
146	Mylan Investigational Site	Skalica		Slovakia	90901
147	Mylan Investigational Site	Sturovo		Slovakia	943 01
148	Mylan Investigational Site	Trebisov		Slovakia	07501
149	Mylan Investigational Site	Zilina		Slovakia	01001
150	Mylan Investigational Site	Bloemfontein	Free State	South Africa	9301
151	Mylan Investigational Site	Johannesburg	Gauteng	South Africa	1501
152	Mylan Investigational Site	Johannesburg	Gauteng	South Africa	1619
153	Mylan Investigational Site	Johannesburg	Gauteng	South Africa	2198
154	Mylan Investigational Site	Krugersdorp	Gauteng	South Africa	1739
155	Mylan Investigational Site	Pretoria	Gauteng	South Africa	0002
156	Mylan Investigational Site	Durban	KwaZulu-Natal	South Africa	4091
157	Mylan Investigational Site	Cape Town	Western Cape	South Africa	7570
158	Mylan Investigational Site	Cape Town	Western Cape	South Africa	7580
159	Mylan Investigational Site	Cape Town	Western Cape	South Africa	7708
160	Mylan Investigational Site	Plymouth	Devon	United Kingdom	PL6 8DH
161	Mylan Investigational Site	Leicester	Leicestershire	United Kingdom	LE5 4PW
162	Mylan Investigational Site	Swansea		United Kingdom	SA6 6NL

Sponsors and Collaborators

• Mylan Inc.
• Mylan GmbH

Investigators

• Principal Investigator: Thomas Blevins, MD, Texas Diabetes & Endocrinology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT02227862
• Other Study ID Numbers: MYL-GAI-3001
• First Posted: Aug 28, 2014
• Last Update Posted: Mar 3, 2022
• Last Verified: Mar 1, 2022

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Glargine

Study Results

Participant Flow

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Period Title: Overall Study
STARTED	280	278
Week 24	269	263
COMPLETED	261	256
NOT COMPLETED	19	22

Baseline Characteristics

Arm/Group Title	Mylan's Insulin Glargine	Lantus®	Total
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Total of all reporting groups
Overall Participants	280	278	558
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	275 98.2%	272 97.8%	547 98%
>=65 years	5 1.8%	6 2.2%	11 2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42 (12.03)	42.2 (11.97)	42.1 (11.99)
Sex: Female, Male (Count of Participants)
Female	116 41.4%	106 38.1%	222 39.8%
Male	164 58.6%	172 61.9%	336 60.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	2 0.7%	2 0.7%	4 0.7%
Black	2 0.7%	5 1.8%	7 1.3%
Caucasian	263 93.9%	265 95.3%	528 94.6%
Hispanic	6 2.1%	3 1.1%	9 1.6%
Other	7 2.5%	3 1.1%	10 1.8%
Region of Enrollment (Count of Participants)
Europe	145 51.8%	145 52.2%	290 52%
North America	126 45%	126 45.3%	252 45.2%
South Africa	9 3.2%	7 2.5%	16 2.9%
Insulin History (Count of Participants)
Yes	280 100%	277 99.6%	557 99.8%
No	0 0%	1 0.4%	1 0.2%
Dosing Time (Count of Participants)
Morning	38 13.6%	40 14.4%	78 14%
Evening	242 86.4%	238 85.6%	480 86%
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	26.435 (3.7058)	26.636 (4.2022)	26.535 (3.9586)
Duration of Diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	18.685 (11.7771)	19.697 (11.2868)	19.206 (11.5411)
Baseline fasting plasma glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	167.4 (68.43)	163.9 (61.61)	165.6 (65.09)
Baseline HbA1c (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	7.37 (0.869)	7.39 (0.843)	7.38 (0.855)
Baseline fasting C-peptide (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	0.298 (0.2291)	0.291 (0.2508)	0.295 (0.2395)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c From Baseline to 24 Weeks
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	277
Least Squares Mean (Standard Error) [percent]	0.14 (0.054)	0.11 (0.054)

2. Secondary Outcome

Title	Summary of Actual and Change From Baseline in HbA1c
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	277
week 24	0.12 (0.599)	0.09 (0.526)
week 52	0.2 (0.633)	0.25 (0.595)

3. Secondary Outcome

Title	Change From Baseline in FPG Over Time
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	277
week 24	-0.81 (4.485)	0.09 (4.507)
week 52	0.23 (4.281)	0.43 (4.455)

4. Secondary Outcome

Title	Change From Baseline in 8-point SMBG Profile Over Time
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	277
week 24	0.038 (2.3751)	-0.095 (1.5012)
week 52	-0.082 (1.5032)	-0.082 (1.5267)

5. Secondary Outcome

Title	Change in Total Daily Insulin Dose Per Unit Body Weight From Baseline Over Time
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	277
week 24	0.0203 (0.09962)	0.0127 (0.10871)
week 52	0.0278 (0.1044)	0.0138 (0.11372)

6. Secondary Outcome

Title	Rate of Hypoglycemic Events Per 30 Days Over Time
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	278
week 24	-5.162 (9.0724)	-4.93 (8.3815)
week 52	-6.241 (9.214)	-5.765 (8.3658)

7. Secondary Outcome

Title	Hypoglycemia Occurrence
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	278
Any hypoglycemic event	273	269
Severe hypoglycemia	11	13
Documented symptomatic hypoglycemia	249	249
Asymptomatic hypoglycemia	246	243
Probable symptomatic hypoglycemia	37	36
Relative hypoglycemia	35	44
Other hypoglycemia	19	19
Unknown	77	71

8. Secondary Outcome

Title	Occurrence of Local and Systematic Reactions
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	278
Local	3	4
Systemic	2	2

9. Secondary Outcome

Title	Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	278
week 24	-0.3063 (7.22075)	0.3592 (7.16624)
week 52	-0.9591 (8.51754)	-1.0634 (8.42794)

10. Secondary Outcome

Title	Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	278
week 24	-0.215 (7.3298)	0.157 (7.411)
week 52	-0.896 (8.5610)	-1.233 (8.623)

11. Secondary Outcome

Title	Change in Cross-reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	278
week 24	-0.363 (7.1081)	0.27 (7.1204)
week 52	-1.132 (8.3911)	-1.21 (8.4096)

12. Secondary Outcome

Title	Change in Cross-reactive Insulin Antibody Percent Binding for Lantus Assay Over Time
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	278
week 24	-0.265 (7.2543)	0.055 (7.3985)
week 52	-1.060 (8.4414)	-1.367 (8.6848)

13. Secondary Outcome

Title	Proportion of Patients With HbA1c < 7%
Time Frame	24 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mylan's Insulin Glargine	Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Measure Participants	280	277
week 24	73 26.1%	84 30.2%
week 52	65 23.2%	61 21.9%

Adverse Events

Time Frame	56 Weeks
Adverse Event Reporting Description	After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Arm/Group Title	Mylan's Insulin Glargine		Lantus®
Arm/Group Description	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.		Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
All Cause Mortality
	Mylan's Insulin Glargine		Lantus®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/280 (0.7%)		1/278 (0.4%)
Serious Adverse Events
	Mylan's Insulin Glargine		Lantus®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/280 (6.4%)		22/278 (7.9%)
Cardiac disorders
Atrial fibrillation	1/280 (0.4%)	1	0/278 (0%)	0
Coronary artery disease	1/280 (0.4%)	1	1/278 (0.4%)	1
Myocardial infarction	0/280 (0%)	0	1/278 (0.4%)	1
Endocrine disorders
Goitre	0/280 (0%)	0	2/278 (0.7%)	2
Hypothyroidism	0/280 (0%)	0	1/278 (0.4%)	1
Eye disorders
Retinal artery occlusion	1/280 (0.4%)	1	0/278 (0%)	0
General disorders
Death	1/280 (0.4%)	1	0/278 (0%)	0
Infections and infestations
Cellulitis	0/280 (0%)	0	1/278 (0.4%)	1
Diverticulitis	1/280 (0.4%)	1	0/278 (0%)	0
Haematoma infection	0/280 (0%)	0	1/278 (0.4%)	1
Pharyngitis	1/280 (0.4%)	1	0/278 (0%)	0
Pneumonia	0/280 (0%)	0	1/278 (0.4%)	1
Pyelonephritis acute	1/280 (0.4%)	1	0/278 (0%)	0
Urosepsis	1/280 (0.4%)	1	0/278 (0%)	0
Viral rash	0/280 (0%)	0	1/278 (0.4%)	1
Injury, poisoning and procedural complications
Femoral neck fracture	1/280 (0.4%)	1	0/278 (0%)	0
Femur fracture	0/280 (0%)	0	1/278 (0.4%)	1
Lower limb fracture	0/280 (0%)	0	1/278 (0.4%)	1
Postoperative respiratory distress	1/280 (0.4%)	1	0/278 (0%)	0
Scapula fracture	0/280 (0%)	0	1/278 (0.4%)	1
Upper limb fracture	0/280 (0%)	0	1/278 (0.4%)	1
Metabolism and nutrition disorders
Hypoglycaemia	7/280 (2.5%)	7	10/278 (3.6%)	10
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis	0/280 (0%)	0	1/278 (0.4%)	1
Osteochondrosis	1/280 (0.4%)	1	0/278 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant oligodendroglioma	0/280 (0%)	0	1/278 (0.4%)	1
Nervous system disorders
Epilepsy	1/280 (0.4%)	1	0/278 (0%)	0
Generalized tonic-clonic seizure	0/280 (0%)	0	2/278 (0.7%)	2
Hypoglycaemic seizure	1/280 (0.4%)	1	0/278 (0%)	0
Ischaemic stroke	0/280 (0%)	0	1/278 (0.4%)	1
Psychiatric disorders
Psychotic disorder	0/280 (0%)	0	1/278 (0.4%)	1
Depression	0/280 (0%)	0	1/278 (0.4%)	1
Renal and urinary disorders
Acute kidney injury	2/280 (0.7%)	2	0/278 (0%)	0
Glomerulonephritis minimal lesion	1/280 (0.4%)	1	0/278 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/280 (0.4%)	1	0/278 (0%)	0
Skin and subcutaneous tissue disorders
Skin ulcer	1/280 (0.4%)	1	0/278 (0%)	0
Vascular disorders
Hypertension	0/280 (0%)	0	1/278 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Mylan's Insulin Glargine		Lantus®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	225/225 (100%)		239/239 (100%)
Cardiac disorders
Tachycardia	0/225 (0%)	0	3/239 (1.3%)	3
Eye disorders
Diabetic retinopathy	2/225 (0.9%)	2	5/239 (2.1%)	5
Gastrointestinal disorders
Nausea	10/225 (4.4%)	10	6/239 (2.5%)	8
Diarrhoea	11/225 (4.9%)	12	4/239 (1.7%)	4
Toothache	4/225 (1.8%)	7	5/239 (2.1%)	5
Vomiting	6/225 (2.7%)	7	2/239 (0.8%)	3
General disorders
Pyrexia	5/225 (2.2%)	6	4/239 (1.7%)	4
Oedema peripheral	4/225 (1.8%)	4	3/239 (1.3%)	3
Fatigue	4/225 (1.8%)	4	2/239 (0.8%)	2
Immune system disorders
Seasonal allergy	2/225 (0.9%)	4	3/239 (1.3%)	3
Infections and infestations
Nasopharyngitis	25/225 (11.1%)	37	39/239 (16.3%)	58
Upper respiratory tract infection	27/225 (12%)	38	33/239 (13.8%)	44
Influenza	12/225 (5.3%)	12	12/239 (5%)	14
Urinary tract infection	9/225 (4%)	13	10/239 (4.2%)	11
Bronchitis	9/225 (4%)	9	8/239 (3.3%)	8
Gastroenteritis	10/225 (4.4%)	10	6/239 (2.5%)	6
Sinusitis	8/225 (3.6%)	10	8/239 (3.3%)	8
Gastroenteritis viral	6/225 (2.7%)	6	7/239 (2.9%)	7
Viral infection	5/225 (2.2%)	5	6/239 (2.5%)	6
Pharyngitis	5/225 (2.2%)	5	2/239 (0.8%)	2
Fungal infection	3/225 (1.3%)	3	3/239 (1.3%)	4
Pharyngitis streptococcal	4/225 (1.8%)	6	2/239 (0.8%)	2
Rhinitis	1/225 (0.4%)	1	5/239 (2.1%)	5
Respiratory tract infection	2/225 (0.9%)	2	3/239 (1.3%)	3
Onychomycosis	1/225 (0.4%)	1	3/239 (1.3%)	3
Respiratory tract infection viral	1/225 (0.4%)	1	3/239 (1.3%)	4
Tonsilitis	3/225 (1.3%)	3	1/239 (0.4%)	1
Vulvovaginal mycotic infection	1/225 (0.4%)	1	3/239 (1.3%)	3
Viral upper respiratory tract infection	3/225 (1.3%)	3	0/239 (0%)	0
Injury, poisoning and procedural complications
Ligament sprain	3/225 (1.3%)	3	2/239 (0.8%)	2
Investigations
Blood creatine phosphokinase increased	1/225 (0.4%)	1	4/239 (1.7%)	4
Blood pressure increased	0/225 (0%)	0	3/239 (1.3%)	3
Metabolism and nutrition disorders
Hypoglycaemia	154/225 (68.4%)	3045	170/239 (71.1%)	3184
Hyperglycaemia	3/225 (1.3%)	3	5/239 (2.1%)	6
Hyperlipidaemia	2/225 (0.9%)	2	3/239 (1.3%)	3
Hyperkalaemia	3/225 (1.3%)	3	0/239 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	9/225 (4%)	13	2/239 (0.8%)	4
Back pain	5/225 (2.2%)	5	6/239 (2.5%)	7
Muscle spasms	4/225 (1.8%)	4	0/239 (0%)	0
Osteoarthritis	3/225 (1.3%)	3	0/239 (0%)	0
Trigger finger	0/225 (0%)	0	3/239 (1.3%)	3
Musculoskeletal pain	5/225 (2.2%)	5	3/239 (1.3%)	3
Nervous system disorders
Headache	5/225 (2.2%)	5	14/239 (5.9%)	20
Carpal tunnel syndrome	4/225 (1.8%)	5	0/239 (0%)	0
Diabetic neuropathy	1/225 (0.4%)	1	3/239 (1.3%)	3
Neuropathy peripheral	3/225 (1.3%)	3	0/239 (0%)	0
Psychiatric disorders
Depression	2/225 (0.9%)	2	3/239 (1.3%)	3
Anxiety	3/225 (1.3%)	3	1/239 (0.4%)	1
Renal and urinary disorders
Microalbuminuria	3/225 (1.3%)	3	0/239 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	6/225 (2.7%)	6	5/239 (2.1%)	5
Oropharyngeal pain	6/225 (2.7%)	6	3/239 (1.3%)	3
Sinus congestion	4/225 (1.8%)	4	4/239 (1.7%)	4
Asthma	5/225 (2.2%)	6	0/239 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	0/225 (0%)	0	4/239 (1.7%)	4
Vascular disorders
Hypertension	9/225 (4%)	9	6/239 (2.5%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.