GALAPAGOS: Insulins Glargine and gluLisine strAtegy Versus Premixed Insulin strAteGy: a cOmparative Study

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT01121835

Collaborator

(none)

934

Enrollment

Locations

Arms

24.9

Duration (Months)

9.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate the superiority of a strategy with insulin glargine in comparison with a strategy including the premixed insulin in term of percentage of patients reaching HbA1c (glycosylated hemoglobin) below 7% at the end of treatment and who do not experience documented symptomatic hypoglycemia (confirmed by a Plasma Glucose (PG) below 56 mg/dL (3.1 mmol/L)) over a 24-week treatment period, in Type 2 diabetes patients failing lifestyle management and oral agents.

Secondary Objectives:

To assess the effect of insulin glargine in comparison with premixed insulin on :

Evolution of HbA1c level during the treatment period Percentage of patients who reach the target of HbA1c < 7 % and who do not experience documented symptomatic hypoglycemia confirmed by a Plasma Glucose (PG) below 70 mg/dL (3.9 mmol/L)
Percentage of patients who reach the target of HbA1c < 6.5% and who do not experience documented symptomatic hypoglycemia confirmed by a PG below 56 mg/dL (3.1 mmol/L)

Percentage of patients who reach the target of HbA1c < 6.5% and who do not experience documented symptomatic hypoglycemia confirmed by a PG below 70 mg/dL (3.9 mmol/L) Evolution of Fasting Plasma Glucose Evolution of 7-point plasma glucose profiles

Evolution of weight
Hypoglycemia occurrence
Dose of insulins
Evolution of liver function
Overall safety

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: INSULIN GLARGINE Drug: INSULIN GLULISINE Drug: PREMIXED INSULIN	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

934 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A 24-week, Open, Multicenter, Comparative Study of 2 Strategies (Including Insulin Glargine Versus Premixed Insulin) for the Therapeutic Management of Patients With Type 2 Diabetes Failing Oral Agents

Study Start Date :

Feb 1, 2010

Actual Primary Completion Date :

Mar 1, 2012

Actual Study Completion Date :

Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin glargine Administered once a day in the evening, at the same time every day. The starting daily dose is 0.2 U/Kg of body weight or 12 U, at the investigator's decision. Insulin glulisine is administered for patients of the insulin glargine group requiring insulin glulisine at week 12 (visit 11). Insulin glulisine is administered prior (10-15 min) to the main meal of the day, which is the meal with highest Post-Prandial Plasma Glucose (PPPG) on the 3 profiles performed before week 12. Starting dose is of 4 units per day.	Drug: INSULIN GLARGINE Pharmaceutical form: solution for injection Route of administration: sub-cutaneous injection Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 ml) Drug: INSULIN GLULISINE Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 mL)
Experimental: Premixed insulin administered once a day (in the evening at dinner) or twice a day (in the morning before breakfast and in the evening at dinner). Starting daily dose will be 6 U at breakfast and 6 U at dinner, if administered twice a day or 12 U at dinner if administered once a day	Drug: PREMIXED INSULIN Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: - 30% soluble insulin aspart and 70 % protamine-crystallised insulin aspart in pre-filled Flexpen for all the countries except Mexico 25 % insulin lispro solution and 75% insulin lispro protamine in cartridges for Humapen Luxura for Mexico only

Arm

Intervention/Treatment

Experimental: Insulin glargine

Administered once a day in the evening, at the same time every day. The starting daily dose is 0.2 U/Kg of body weight or 12 U, at the investigator's decision. Insulin glulisine is administered for patients of the insulin glargine group requiring insulin glulisine at week 12 (visit 11). Insulin glulisine is administered prior (10-15 min) to the main meal of the day, which is the meal with highest Post-Prandial Plasma Glucose (PPPG) on the 3 profiles performed before week 12. Starting dose is of 4 units per day.

Drug: INSULIN GLARGINE

Pharmaceutical form: solution for injection Route of administration: sub-cutaneous injection Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 ml)

Drug: INSULIN GLULISINE

Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 mL)

Experimental: Premixed insulin

administered once a day (in the evening at dinner) or twice a day (in the morning before breakfast and in the evening at dinner). Starting daily dose will be 6 U at breakfast and 6 U at dinner, if administered twice a day or 12 U at dinner if administered once a day

Drug: PREMIXED INSULIN

Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: - 30% soluble insulin aspart and 70 % protamine-crystallised insulin aspart in pre-filled Flexpen for all the countries except Mexico 25 % insulin lispro solution and 75% insulin lispro protamine in cartridges for Humapen Luxura for Mexico only

Outcome Measures

Primary Outcome Measures

Percentage of patients with Glycosylated Haemoglobin (HbA1c) <7% with no documented symptomatic hypoglycemia (confirmed by a Plasma Glucose (PG) ≤ 56 mg/dL [3.1 mmol/L] [From baseline (visit 2, week 0) to visit 14 (week 24)]

Secondary Outcome Measures

7-point plasma glucose (PG) profile recorded on 3 consecutive days [From baseline (visit 2, week 0) to visit 14 (week 24)]
Self-monitored PG (Plasma Glucose) values over 3 consecutive days [before visit 4 (week 2)]
Self-monitored PG (Plasma Glucose) values over 3 consecutive days [before visit 8 (week 6)]
Self-monitored PG (Plasma Glucose) values over 3 consecutive days [before visit 12 (week 16)]
Weight and supine blood pressure [From baseline (visit 2, week 0) to visit 14 (week 24)]
Insulin doses of the day before each visit [from visit 3 (week 1) to visit 14 (week 24)]
Biochemistry and lipid profile [From baseline (visit 2, week 0) to visit 14 (week 24)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Type 2 diabetes diagnosed for more than 1 year
Insulin naïve
Treated with lifestyle interventions and oral antidiabetic drugs, at least metformin at the maximum tolerated dose (with a minimum dose of 1g/day), for at least 3 months
HbA1c ≥ 7.0 % and ≤ 10.5%
Body mass index (BMI) ≤ 40 kg/m2
Ability and willingness to perform plasma glucose (PG) monitoring using the sponsor-provided glucose meter and to complete the patient diary
Willingness and ability to comply with the study protocol
Signed informed consent obtained prior any study procedure

Exclusion criteria:

Treatment with glucagon-like peptide-1 (GLP-1) agonists in the 3 months prior to study entry
Previous treatment with insulin (except for treatment of gestational diabetes or brief treatment with insulin for less than 1 week)
Diabetes other than type 2 diabetes (e.g. type 1 diabetes, diabetes secondary to pancreatic disorders, drug or chemical agent intake)
Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method)
Hospitalized patient (except for routine diabetes check-up)
Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by retina examination, in the 2 years prior to study entry
History of sensitivity to the study drugs or to drugs with a similar chemical structure
Impaired renal function: creatinine clearance < 60ml/min
Impaired liver function (ALT, AST > 3 x upper limit of normal range)
Severe gastro-intestinal disease
Treatment with corticosteroids with potential systemic action within the 3 months prior to study entry
Likelihood of requiring treatments during the study which are not permitted
Treatment with an investigational product in the 30 days prior to study entry
Alcohol or drug abuse within the last 5 years

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Investigational Site Number 040-004	Sankt Stefan	Austria	A-8511
2	Investigational Site Number 040-002	Vienna	Austria	A-1030
3	Investigational Site Number 040-001	Vienna	Austria
4	Investigational Site Number 040-003	Vienna	Austria
5	Investigational Site Number 076002	Belém	Brazil	66073-000
6	Investigational Site Number 076005	Curitiba	Brazil	80060-900
7	Investigational Site Number 076004	Fortaleza	Brazil	60430-370
8	Investigational Site Number 076001	Porto Alegre	Brazil	90035-001
9	Investigational Site Number 076003	São Paulo	Brazil	04024-002
10	Investigational Site Number 156004	Beijing	China
11	Investigational Site Number 156005	Beijing	China
12	Investigational Site Number 156006	Beijing	China
13	Investigational Site Number 156011	Chongqing	China
14	Investigational Site Number 156009	Dalian	China
15	Investigational Site Number 156008	Guangzhou	China
16	Investigational Site Number 156012	Haikou	China
17	Investigational Site Number 156007	Nanjing	China
18	Investigational Site Number 156001	Shanghai	China
19	Investigational Site Number 156002	Shanghai	China
20	Investigational Site Number 156003	Shanghai	China
21	Investigational Site Number 156010	Shenyang	China
22	Investigational Site Number 170001	Bogota	Colombia
23	Investigational Site Number 170002	Bogota	Colombia
24	Investigational Site Number 170003	Bucaramanga	Colombia
25	Investigational Site Number 170005	Manizales	Colombia	170
26	Investigational Site Number 170004	Pereira	Colombia	170
27	Investigational Site Number 208-001	Hvidovre	Denmark	2650
28	Investigational Site Number 208-003	København NV.	Denmark	2400
29	Investigational Site Number 208-002	København S.	Denmark	2300
30	Investigational Site Number 300006	Alexandroupolis	Greece	68100
31	Investigational Site Number 300001	Athens	Greece
32	Investigational Site Number 300002	Athens	Greece
33	Investigational Site Number 300003	Athens	Greece
34	Investigational Site Number 300004	Athens	Greece
35	Investigational Site Number 300005	Iraklion	Greece	71001
36	Investigational Site Number 300011	Maroussi, Athens	Greece	15123
37	Investigational Site Number 300008	Thessaloniki	Greece	546 36
38	Investigational Site Number 300010	Thessaloniki	Greece	56429
39	Investigational Site Number 300007	Thessaloniki	Greece	57010
40	Investigational Site Number 356008	Bangalore	India	560043
41	Investigational Site Number 356003	Bangalore	India	560052
42	Investigational Site Number 356007	Bangalore	India	560092
43	Investigational Site Number 356006	Bhubaneshwar	India	751019
44	Investigational Site Number 356001	Hyderabad	India	500034
45	Investigational Site Number 356005	Hyderabad	India	500034
46	Investigational Site Number 356004	Trivandrum	India
47	Investigational Site Number 380-010	Catania	Italy	95122
48	Investigational Site Number 380-008	Catania	Italy	95124
49	Investigational Site Number 380-006	Colleferro	Italy	00034
50	Investigational Site Number 380-007	Foggia	Italy	71100
51	Investigational Site Number 380-005	Forlì	Italy
52	Investigational Site Number 380-001	Genova	Italy	16132
53	Investigational Site Number 380-011	Merano	Italy	39100
54	Investigational Site Number 380-009	Napoli	Italy	80131
55	Investigational Site Number 380-012	Napoli	Italy	80131
56	Investigational Site Number 380-004	Parma	Italy	43100
57	Investigational Site Number 410004	Ansan-si, Kyouggi-do	Korea, Republic of
58	Investigational Site Number 410003	Koyang-si	Korea, Republic of
59	Investigational Site Number 410001	Seoul	Korea, Republic of
60	Investigational Site Number 410002	Seoul	Korea, Republic of
61	Investigational Site Number 001	Kuwait	Kuwait
62	Investigational Site Number 484004	Aguascalientes	Mexico	20020
63	Investigational Site Number 484001	Aguascalientes	Mexico	20230
64	Investigational Site Number 484003	Guadalajara	Mexico	44650
65	Investigational Site Number 484002	Guadalajara	Mexico	44680
66	Investigational Site Number 484005	Puebla	Mexico	72000
67	Investigational Site Number 642001	Iasi	Romania	700111
68	Investigational Site Number 642002	Iasi	Romania
69	Investigational Site Number 642003	Oradea	Romania	410169
70	Investigational Site Number 724001	Avila	Spain	05071
71	Investigational Site Number 724002	Barcelona	Spain	08022
72	Investigational Site Number 724008	Galdakao	Spain	48960
73	Investigational Site Number 724007	Lugo	Spain	27004
74	Investigational Site Number 724004	Madrid	Spain	28805
75	Investigational Site Number 724009	Pamplona	Spain	31008
76	Investigational Site Number 724005	Santa Coloma de Gramanet	Spain	8923
77	Investigational Site Number 724003	Sevilla	Spain	41010
78	Investigational Site Number 724006	Valencia	Spain	46010
79	Investigational Site Number 158004	Changhua County	Taiwan
80	Investigational Site Number 158003	Hsintien	Taiwan	23137
81	Investigational Site Number 158007	Kaohsiung Hsien,	Taiwan
82	Investigational Site Number 158006	New Taipei city	Taiwan
83	Investigational Site Number 158009	Taichung City	Taiwan
84	Investigational Site Number 158001	Taichung	Taiwan	407
85	Investigational Site Number 158005	Tainan	Taiwan
86	Investigational Site Number 158002	Taipei	Taiwan
87	Investigational Site Number 792-013	Ankara	Turkey	06100
88	Investigational Site Number 792-009	Canakkale	Turkey	17110
89	Investigational Site Number 792-006	Diyarbakir	Turkey	21830
90	Investigational Site Number 792-004	Istanbul	Turkey	34098
91	Investigational Site Number 792-001	Izmir	Turkey	35340
92	Investigational Site Number 792-016	Konya	Turkey
93	Investigational Site Number 792-007	Sivas	Turkey	58140
94	Investigational Site Number 792-005	Trabzon	Turkey
95	Investigational Site Number 792-002	Van	Turkey	65080
96	Investigational Site Number 784-001	Dubai	United Arab Emirates