STEADFAST: Vildagliptin Compared to Gliclazide as Dual Therapy With Metformin in Muslim Patients With Type 2 Diabetes Fasting During Ramadan

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01758380

Collaborator

(none)

557

Enrollment

Locations

Arms

Duration (Months)

8.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate vildagliptin as compared to gliclazide, given in combination with metformin in Muslim patients with type 2 diabetes fasting during Ramadan.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Vildagliptin Drug: Gliclazide Drug: Metformin Drug: Placebo to Gliclazide Drug: Placebo to Vildagliptin	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

557 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Double Blind, Double Dummy, Randomised, Multi-centre Study to Assess the Tolerability and Efficacy Profile of Vildagliptin Compared to Gliclazide as Dual Therapy With Metformin in Muslim Patients With Type 2 Diabetes Fasting During Ramadan

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Sep 1, 2013

Actual Study Completion Date :

Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vildagliptin + placebo to Gliclazide Vildagliptin tablets will be given at 50mg twice daily (bid). Placebo to Gliclazide capsules will be given at an equivalent dose to previous sulfonylurea in multiples of 80mg only (80-320 mg/day). Patients will continue their open-label metformin therapy at dosage between 1500-2500 mg daily.	Drug: Vildagliptin Patients will be instructed to take Vildagliptin tablets at a fixed dose of 50 mg twice daily (double blind therapy) Other Names: Galvus Drug: Metformin Patients in both arms will take Metformin at a dose between 1500mg-2500mg per day, in an open label fashion Drug: Placebo to Gliclazide Patients will be instructed to take the Gliclazide matching placebo capsules at an equivalent dose to previous sulfonylurea in multiples of 80mg only (double blind therapy)
Active Comparator: Gliclazide + placebo to Vildagliptin Gliclazide capsules will be given in multiples of 80 mg (80-320 mg/day) at a dose equivalent to previous sulfonylurea dose, unless at the investigator's discretion it could be up-titrated to the next available dose (if HbA1c is higher than 7.5%). Placebo to Vildagliptin tablets will be given at 50mg twice daily (bid). Patients will continue their open-label metformin therapy at dosage between 1500-2500 mg daily.	Drug: Gliclazide Patients will be instructed to take Gliclazide capsules at an equivalent dose to previous sulfonylurea in multiples of 80mg only (double blind therapy) Drug: Metformin Patients in both arms will take Metformin at a dose between 1500mg-2500mg per day, in an open label fashion Drug: Placebo to Vildagliptin Patients will be instructed to take Vildagliptin matching placebo tablets at a fixed dose of 50 mg twice daily (double blind therapy).

Arm

Intervention/Treatment

Experimental: Vildagliptin + placebo to Gliclazide

Vildagliptin tablets will be given at 50mg twice daily (bid). Placebo to Gliclazide capsules will be given at an equivalent dose to previous sulfonylurea in multiples of 80mg only (80-320 mg/day). Patients will continue their open-label metformin therapy at dosage between 1500-2500 mg daily.

Drug: Vildagliptin

Patients will be instructed to take Vildagliptin tablets at a fixed dose of 50 mg twice daily (double blind therapy)

Other Names:

Galvus

Drug: Metformin

Patients in both arms will take Metformin at a dose between 1500mg-2500mg per day, in an open label fashion

Drug: Placebo to Gliclazide

Patients will be instructed to take the Gliclazide matching placebo capsules at an equivalent dose to previous sulfonylurea in multiples of 80mg only (double blind therapy)

Active Comparator: Gliclazide + placebo to Vildagliptin

Gliclazide capsules will be given in multiples of 80 mg (80-320 mg/day) at a dose equivalent to previous sulfonylurea dose, unless at the investigator's discretion it could be up-titrated to the next available dose (if HbA1c is higher than 7.5%). Placebo to Vildagliptin tablets will be given at 50mg twice daily (bid). Patients will continue their open-label metformin therapy at dosage between 1500-2500 mg daily.

Drug: Gliclazide

Patients will be instructed to take Gliclazide capsules at an equivalent dose to previous sulfonylurea in multiples of 80mg only (double blind therapy)

Drug: Metformin

Patients in both arms will take Metformin at a dose between 1500mg-2500mg per day, in an open label fashion

Drug: Placebo to Vildagliptin

Patients will be instructed to take Vildagliptin matching placebo tablets at a fixed dose of 50 mg twice daily (double blind therapy).

Outcome Measures

Primary Outcome Measures

Percentage of patients experiencing at least one Hypoglycaemic Event (HE) during the Ramadan fasting period to test superiority [1 month]

Secondary Outcome Measures

Percentage of patients without an increase in HbA1c (≤ 0.3%) and with no Hypoglycaemic Events (HEs) [visit 3 (anytime from week -4 to day -1 before start of Ramadan) to visit 4 (within 4 weeks post-Ramadan fasting period) (minimum 4.5 weeks to maximum 12 weeks) for HbA1c; and during 1 month (Ramadan) for HEs]
Change from baseline to endpoint in glycosylated hemoglobin (HbA1c) [baseline to visit 4 (within 4 weeks post-Ramadan fasting period) (minimum 12.5 weeks to maximum 30 weeks)]
Endpoint is defined as the visit 4 (post-Ramadan) measurement or the last observation obtained during or after Ramadan, prior to or at initiation of rescue medication
Change from visit 3 (pre-Ramadan visit) to endpoint in glycosylated hemoglobin (HbA1c) [visit 3 (anytime from week-4 to day-1 before start of Ramadan) to visit 4 (within 4 weeks post-Ramadan fasting period) (minimum 4.5 weeks to maximum 12 weeks)]
Endpoint is defined as the visit 4 (post-Ramadan) measurement or the last observation obtained during or after Ramadan, prior to or at initiation of rescue medication
Proportion of patients experiencing severe hypoglycemic events during the Ramadan fasting period [1 month]
mean amplitude of glycemic excursions (MAGE) to measure glucose fluctuations during the day [72 hours]
assessed in a selected subgroup of patients
Treatment adherence during the Ramadan fasting period [1 month]
Change from visit 3 (pre-Ramadan visit) to endpoint in body weight [From visit 3 (anytime from week-4 to day-1 before start of Ramadan) to visit 4 (within 4 weeks post-Ramadan fasting period) (minimum 4.5 weeks to maximum 12 weeks)]
Endpoint is defined as the visit 4 (post-Ramadan) measurement or the last observation obtained during or after Ramadan, prior to or at initiation of rescue medication
Number of unscheduled visit to health care professional [From visit 3 (anytime from week-4 to day-1 before start of Ramadan) to visit 4 (within 4 weeks post-Ramadan fasting period) (minimum 4.5 weeks to maximum 12 weeks)]
Number of days fasted during the Ramadan fasting period [1 month]
Number of patients with treatment emergent adverse events (AEs), serious AEs, discontinuation due to AEs, deaths or laboratory abnormalities as assessment of safety and tolerability [Baseline to visit 4 (within 4 weeks post-Ramadan fasting period) (minimum 12.5 weeks to maximum 30 weeks)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed Type 2 Diabetes diagnosis
Plan to fast during Ramadan
Treated with a combination of metformin and an Sulfonylurea (SU) for at least 12 weeks and HbA1c ≤8.5% at Visit 1
Taking a sulfonylurea treatment for less than 3 years prior to Visit 1
Body mass index (BMI) ≥22 and ≤45 kg/m2 at Visit 1

Exclusion Criteria:

Pregnant or nursing (lactating) women
History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
Patients who are taking any other anti-diabetes drug (oral or injection) other than metformin and an SU component.
Inability to comply with the study procedures or medications.

"Other protocol-defined inclusion/exclusion criteria may apply"

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Frederiksberg		Denmark	1819
2	Novartis Investigative Site	Alexandria		Egypt	21131
3	Novartis Investigative Site	Cairo		Egypt	11566
4	Novartis Investigative Site	Augsburg		Germany	86150
5	Novartis Investigative Site	Augsburg		Germany	86159
6	Novartis Investigative Site	Bad Oeynhausen		Germany	32549
7	Novartis Investigative Site	Berlin		Germany	10997
8	Novartis Investigative Site	Dortmund		Germany	44137
9	Novartis Investigative Site	Einbeck		Germany	37574
10	Novartis Investigative Site	Loehne		Germany	32584
11	Novartis Investigative Site	Meine		Germany	38527
12	Novartis Investigative Site	München		Germany	80339
13	Novartis Investigative Site	Saarlouis		Germany	66740
14	Novartis Investigative Site	Malang	East Java	Indonesia	65111
15	Novartis Investigative Site	Surabaya	East Java	Indonesia	60286
16	Novartis Investigative Site	Padang	Sumatera Barat	Indonesia	25127
17	Novartis Investigative Site	Jakarta		Indonesia	10220
18	Novartis Investigative Site	Jakarta		Indonesia	10430
19	Novartis Investigative Site	Amman		Jordan	11196
20	Novartis Investigative Site	Kuwait		Kuwait	1180
21	Novartis Investigative Site	Beirut		Lebanon	1107 2020
22	Novartis Investigative Site	Beirut		Lebanon
23	Novartis Investigative Site	Hazmieh		Lebanon	470
24	Novartis Investigative Site	Saida		Lebanon
25	Novartis Investigative Site	Kota Bahru	Kelantan	Malaysia	16150
26	Novartis Investigative Site	Kuala Lumpur		Malaysia	59100
27	Novartis Investigative Site	Krasnodar		Russian Federation	350063
28	Novartis Investigative Site	Penza		Russian Federation	440026
29	Novartis Investigative Site	Rostov on Don		Russian Federation	344000
30	Novartis Investigative Site	Rostov-on-Don		Russian Federation	344718
31	Novartis Investigative Site	Saratov		Russian Federation	410012
32	Novartis Investigative Site	St. Petersburg		Russian Federation	191015
33	Novartis Investigative Site	St.- Petersburg		Russian Federation	199034
34	Novartis Investigative Site	Ufa		Russian Federation	450000
35	Novartis Investigative Site	Dammam		Saudi Arabia	40145
36	Novartis Investigative Site	Riyadh		Saudi Arabia	11426
37	Novartis Investigative Site	Singapore		Singapore	440080
38	Novartis Investigative Site	Singapore		Singapore	545025
39	Novartis Investigative Site	Singapore		Singapore	659164
40	Novartis Investigative Site	Málaga	Andalucia	Spain	29010
41	Novartis Investigative Site	Barcelona	Cataluña	Spain	08001
42	Novartis Investigative Site	Girona	Cataluña	Spain	17007
43	Novartis Investigative Site	Salt	Cataluña	Spain	17190
44	Novartis Investigative Site	Santa Coloma de Gramanet	Cataluña	Spain	08923
45	Novartis Investigative Site	Vic	Cataluña	Spain	08500
46	Novartis Investigative Site	Ceuta		Spain	51002
47	Novartis Investigative Site	Melilla		Spain	52005
48	Novartis Investigative Site	Le Belvedere - Tunis	Tunisie	Tunisia	1002
49	Novartis Investigative Site	Sfax	Tunisie	Tunisia	3029
50	Novartis Investigative Site	Tunis	Tunisie	Tunisia	1007
51	Novartis Investigative Site	Monastir		Tunisia	5000
52	Novartis Investigative Site	Sousse		Tunisia	4000
53	Novartis Investigative Site	Tunis		Tunisia	1007
54	Novartis Investigative Site	Tunis		Tunisia
55	Novartis Investigative Site	Diskapi / Ankara		Turkey	06770
56	Novartis Investigative Site	Istanbul		Turkey	34093
57	Novartis Investigative Site	Istanbul		Turkey	34304
58	Novartis Investigative Site	Izmir		Turkey	35380
59	Novartis Investigative Site	Kahramanmaras		Turkey	46050
60	Novartis Investigative Site	Dubai		United Arab Emirates
61	Novartis Investigative Site	Leicester	Leicestershire	United Kingdom	LE5 4PW
62	Novartis Investigative Site	Birmingham		United Kingdom	B15 2TT
63	Novartis Investigative Site	Birmingham		United Kingdom	B8 3Sw
64	Novartis Investigative Site	Birmingham		United Kingdom	B9 5SS
65	Novartis Investigative Site	Bolton		United Kingdom	BL4 0JR
66	Novartis Investigative Site	Derby		United Kingdom	DE22 3NE
67	Novartis Investigative Site	London		United Kingdom	W6 7HY
68	Novartis Investigative Site	Manchester		United Kingdom	M13 9WL