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

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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Vildagliptin; Drug: Metformin; Drug: Placebo to Gliclazide; Drug: Gliclazide; Drug: Placebo to Vildagliptin

• Study Type: Interventional
• Enrollment (Actual): 557
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg, Denmark, 1819
    • Novartis Investigative Site
• Egypt
  • Alexandria, Egypt, 21131
    • Novartis Investigative Site
  • Cairo, Egypt, 11566
    • Novartis Investigative Site
• Germany
  • Augsburg, Germany, 86150
    • Novartis Investigative Site
  • Augsburg, Germany, 86159
    • Novartis Investigative Site
  • Bad Oeynhausen, Germany, 32549
    • Novartis Investigative Site
  • Berlin, Germany, 10997
    • Novartis Investigative Site
  • Dortmund, Germany, 44137
    • Novartis Investigative Site
  • Einbeck, Germany, 37574
    • Novartis Investigative Site
  • Loehne, Germany, 32584
    • Novartis Investigative Site
  • Meine, Germany, 38527
    • Novartis Investigative Site
  • München, Germany, 80339
    • Novartis Investigative Site
  • Saarlouis, Germany, 66740
    • Novartis Investigative Site
• Indonesia
  • Jakarta, Indonesia, 10220
    • Novartis Investigative Site
  • Jakarta, Indonesia, 10430
    • Novartis Investigative Site
  • East Java
    • Malang, East Java, Indonesia, 65111
      • Novartis Investigative Site
    • Surabaya, East Java, Indonesia, 60286
      • Novartis Investigative Site
  • Sumatera Barat
    • Padang, Sumatera Barat, Indonesia, 25127
      • Novartis Investigative Site
• Jordan
  • Amman, Jordan, 11196
    • Novartis Investigative Site
• Kuwait
  • Kuwait, Kuwait, 1180
    • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon, 1107 2020
    • Novartis Investigative Site
  • Beirut, Lebanon
    • Novartis Investigative Site
  • Hazmieh, Lebanon, 470
    • Novartis Investigative Site
  • Saida, Lebanon
    • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • Kelantan
    • Kota Bahru, Kelantan, Malaysia, 16150
      • Novartis Investigative Site
• Russian Federation
  • Krasnodar, Russian Federation, 350063
    • Novartis Investigative Site
  • Penza, Russian Federation, 440026
    • Novartis Investigative Site
  • Rostov on Don, Russian Federation, 344000
    • Novartis Investigative Site
  • Rostov-on-Don, Russian Federation, 344718
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410012
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 191015
    • Novartis Investigative Site
  • St.- Petersburg, Russian Federation, 199034
    • Novartis Investigative Site
  • Ufa, Russian Federation, 450000
    • Novartis Investigative Site
• Saudi Arabia
  • Dammam, Saudi Arabia, 40145
    • Novartis Investigative Site
  • Riyadh, Saudi Arabia, 11426
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 440080
    • Novartis Investigative Site
  • Singapore, Singapore, 545025
    • Novartis Investigative Site
  • Singapore, Singapore, 659164
    • Novartis Investigative Site
• Spain
  • Ceuta, Spain, 51002
    • Novartis Investigative Site
  • Melilla, Spain, 52005
    • Novartis Investigative Site
  • Andalucia
    • Málaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08001
      • Novartis Investigative Site
    • Girona, Cataluña, Spain, 17007
      • Novartis Investigative Site
    • Salt, Cataluña, Spain, 17190
      • Novartis Investigative Site
    • Santa Coloma de Gramanet, Cataluña, Spain, 08923
      • Novartis Investigative Site
    • Vic, Cataluña, Spain, 08500
      • Novartis Investigative Site
• Tunisia
  • Monastir, Tunisia, 5000
    • Novartis Investigative Site
  • Sousse, Tunisia, 4000
    • Novartis Investigative Site
  • Tunis, Tunisia
    • Novartis Investigative Site
  • Tunis, Tunisia, 1007
    • Novartis Investigative Site
  • Tunisie
    • Le Belvedere - Tunis, Tunisie, Tunisia, 1002
      • Novartis Investigative Site
    • Sfax, Tunisie, Tunisia, 3029
      • Novartis Investigative Site
    • Tunis, Tunisie, Tunisia, 1007
      • Novartis Investigative Site
• Turkey
  • Diskapi / Ankara, Turkey, 06770
    • Novartis Investigative Site
  • Istanbul, Turkey, 34093
    • Novartis Investigative Site
  • Istanbul, Turkey, 34304
    • Novartis Investigative Site
  • Izmir, Turkey, 35380
    • Novartis Investigative Site
  • Kahramanmaras, Turkey, 46050
    • Novartis Investigative Site
• United Arab Emirates
  • Dubai, United Arab Emirates
    • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Novartis Investigative Site
  • Birmingham, United Kingdom, B15 2TT
    • Novartis Investigative Site
  • Birmingham, United Kingdom, B8 3Sw
    • Novartis Investigative Site
  • Bolton, United Kingdom, BL4 0JR
    • Novartis Investigative Site
  • Derby, United Kingdom, DE22 3NE
    • Novartis Investigative Site
  • London, United Kingdom, W6 7HY
    • Novartis Investigative Site
  • Manchester, United Kingdom, M13 9WL
    • Novartis Investigative Site
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE5 4PW
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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"

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Metformin; Patients in both arms will take Metformin at a dose between 1500mg-2500mg per day, in an open label fashion; 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: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients experiencing at least one Hypoglycaemic Event (HE) during the Ramadan fasting period to test superiority	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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	baseline to visit 4 (within 4 weeks post-Ramadan fasting period) (minimum 12.5 weeks to maximum 30 weeks)
Change from visit 3 (pre-Ramadan visit) to endpoint in glycosylated hemoglobin (HbA1c)	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	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)
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	assessed in a selected subgroup of patients	72 hours
Treatment adherence during the Ramadan fasting period		1 month
Change from visit 3 (pre-Ramadan visit) to endpoint in body weight	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	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 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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Hassanein M, Abdallah K, Schweizer A. A double-blind, randomized trial, including frequent patient-physician contacts and Ramadan-focused advice, assessing vildagliptin and gliclazide in patients with type 2 diabetes fasting during Ramadan: the STEADFAST study. Vasc Health Risk Manag. 2014 May 28;10:319-26. doi: 10.2147/VHRM.S64038. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: December 24, 2012
• First Submitted That Met QC Criteria: December 24, 2012
• First Posted (Estimate): January 1, 2013

Study Record Updates

• Last Update Posted (Estimate): October 17, 2013
• Last Update Submitted That Met QC Criteria: October 16, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Hypoglycemia; Type 2 Diabetes Mellitus; Vildagliptin; Ramadan
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Gliclazide; Vildagliptin
• Other Study ID Numbers: CLAF237A2411; 2011-005499-41 (EudraCT Number)