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Trial record 56 of 61 for:    Lixisenatide

The Effect of Soliqua on Glucose Variability in Type 2 Patients Among South Asians (VARIATION 2 SA)

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ClinicalTrials.gov Identifier: NCT03819790
Recruitment Status : Recruiting
First Posted : January 29, 2019
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
LMC Diabetes & Endocrinology Ltd.

Brief Summary:
The overall objective of this study is to compare the effects of Soliqua, a titratable combination of insulin and GLP-1 receptor agonist in a single pen versus Glargine U100 insulin (Basaglar or Lantus) and gliclazide MR, both added to metformin, on measures of glucose variability using masked CGM data among people of South Asian origin living in Canada with type 2 diabetes (T2DM).

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Basal insulin glargine and lixisenatide Drug: Basal insulin Basaglar/Lantus + gliclazide MR Drug: Metformin Phase 4

Detailed Description:
The VARIATION 2 SA study is a prospective, open-label, randomized controlled, multi-centre trial to compare the efficacy of two insulin initiation approaches (Soliqua vs Glargine U100 insulin (Basaglar or Lantus) + gliclazide MR) added to maximum tolerated metformin on glucose variability (using masked CGM) in South Asians with T2DM who will initiate insulin therapy with HbA1c of 7.1-11% (inclusive). After giving informed consent and being assessed by eligibility, the patient will stop other oral hypoglycemic agents except metformin (SGLT2 inhibitor may be continued if the patient has cardiovascular diseases history) and enter a 1-week run-in phase with Basaglar or Lantus insulin. During this week (considered as baseline), the patient will: 1) be administered Basaglar or Lantus insulin at an initial dose of 10 units in the morning and increase 1 U/day if fasting glucose >5.5 mmol/L; 2) complete 2 questionnaires to assess the patient-reported outcomes (PROs); 3) wear a masked continuous glucose monitor (CGM) to assess glucose variability; 4) record carbohydrate intake for at least 3 consecutive days. If a patient demonstrates good adherence to Basaglar or Lantus insulin therapy, proper CGM wearing and proper record of carbohydrate intake, and is willing to adhere to insulin treatment will be randomly assigned (1:1) to receive either Soliqua or Glargine U100 insulin (Basaglar or Lantus) + gliclazide MR treatment. The patients will initiate insulin Soliqua or Basaglar/Lantus at their end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by 1 U/day until fasting glucose reaches 4-5.5 mmol/L. In the next 12 weeks, the patients will be optimized their insulin doses via clinic visits or phone calls. They will also be instructed to record their daily fasting glucose, insulin dose, hypoglycemic episodes and any adverse events in a logbook. The primary outcome is to compare the difference of average percentage of Time in Range (4.0-10.0 mmol/L) within 24 hours over the CGM period between two treatments at week 13 after randomization. The co-primary is to compare the difference average percentage of Time in Range (4.0-10.0 mmol/L) within 12 hours (6 AM- 6 PM) over the CGM period between two treatments at week 13 after randomization. The secondary outcomes include the differences on other measurements of glucose variability and patient-reported outcomes (PROs).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be randomized into either of two arms by an interactive system in a 1:1 ratio. Randomization will be stratified based on the use of sodium-glucose co-transporter-2 (SGLT2) inhibitors.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Variability of Glucose Assessed in a Randomized Trial Comparing the Initiation of A Treatment Approach With Biosimilar Basal Insulin Analog Or a Titratable iGlarLixi combinatioN in Type 2 Diabetes Among South Asian Subjects (VARIATION 2 SA Trial)
Actual Study Start Date : October 2, 2018
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Insulin Glargine + GLP-1 RA
Insulin Soliqua (a titratable combination of insulin Glargine + GLP-1 RA) will be administered at the subject's end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by one unit per day until fasting glucose level of 4-5.5 mmol/L is obtained, with or without metformin.
Drug: Basal insulin glargine and lixisenatide
Soliqua (insulin glargine and lixisenatide): a titratable combination of long-acting basal insulin glargine and lixisenatide (Glucagon-like peptide-1 receptor agonist)

Drug: Metformin
Patients can be administered with most tolerant dose of metformin

Active Comparator: Basaglar/Lantus + gliclazide MR
Basal insulin Basaglar/Lantus will be administered at the subject's end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by one unit per day until fasting glucose level of 4-5.5 mmol/L is obtained, with gliclazide MR 60 mg OD, with or without metformin.
Drug: Basal insulin Basaglar/Lantus + gliclazide MR
basal long-acting insulin Basaglar/Lantus with gliclazide MR 60 mg OD

Drug: Metformin
Patients can be administered with most tolerant dose of metformin




Primary Outcome Measures :
  1. Time in range at week 13 [ Time Frame: 7 days ]
    Time with CGM glucose between 4.0 - 10.0 mmol/L within 24 hours over the 7-day CGM period at week 13 after randomization

  2. Time in range within 12-hours (6 AM -6 PM) at week 13 [ Time Frame: 7 days ]
    Time with CGM glucose between 4.0 - 10.0 mmol/L within 12-hours (6 AM -6 PM) over the 7-day CGM period at week 13 after randomization


Secondary Outcome Measures :
  1. Daily glucose standard deviation (SD) at week 13 [ Time Frame: 7 days ]
    Daily SD of CGM glucose over the 7-day CGM period at week 13 after randomization

  2. Overall SD of CGM glucose at week 13 [ Time Frame: 7 days ]
    Overall SD of CGM glucose over the 7-day CGM period at week 13 after randomization

  3. Mean of glucose at week 13 [ Time Frame: 7 days ]
    Mean of CGM glucose over the 7-day CGM period at week 13 after randomization

  4. Frequency of hypoglycemia at week 13 [ Time Frame: 7 days ]
    Number of hypoglycemic event which is defined as CGM glucose <4.0 mmol/L for at least 15 mins (3 consecutive CGM readings) over the 7-day CGM period at week 13 after randomization

  5. Time in hypoglycemia at week 13 [ Time Frame: 7 days ]
    Time with CGM glucose < 4.0 mmol/L over the 7-day CGM period at week 13 after randomization

  6. Frequency of hyperglycemia at week 13 [ Time Frame: 7 days ]
    Number of hyperglycemic event which is defined as CGM glucose >10.0 mmol/L at least 15 mins (3 consecutive CGM readings) over the 7-day CGM period at week 13 after randomization

  7. Time in hyperglycemia at week 13 [ Time Frame: 7 days ]
    Time with CGM glucose >10.0 mmol/L over the 7-day CGM period at week 13 after randomization

  8. Daily glucose standard deviation (SD) within 12 hours (6AM-6PM) at week 13 [ Time Frame: 7 days ]
    Daily SD of CGM glucose within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization

  9. Overall SD of glucose within 12 hours (6AM-6PM) at week 13 [ Time Frame: 7 days ]
    Overall SD of CGM glucose within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization

  10. Mean of glucose within 12 hours (6AM-6PM) at week 13 [ Time Frame: 7 days ]
    Mean of CGM glucose within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization

  11. Frequency of hypoglycemia within 12 hours (6AM-6PM) at week 13 [ Time Frame: 7 days ]
    Number of hypoglycemic event which is defined as CGM glucose <4.0 mmol/L for at least 15 mins (3 consecutive CGM readings) within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization

  12. Time in hypoglycemia within 12 hours (6AM-6PM) at week 13 [ Time Frame: 7 days ]
    Time with CGM glucose <4.0 mmol/L within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization

  13. Frequency of hyperglycemia within 12 hours (6AM-6PM) at week 13 [ Time Frame: 7 days ]
    Number of hypoglycemic event which is defined as CGM glucose >10.0 mmol/L for at least 15 mins (3 consecutive CGM readings) within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization

  14. Time in hyperglycemia within 12 hours (6AM-6PM) at week 13 [ Time Frame: 7 days ]
    Time with CGM glucose >10.0 mmol/L within 12 hours (6AM-6PM) over the 7-day CGM period at week 13 after randomization

  15. A1C mean at week 13 [ Time Frame: Week 13 ]
    Average of A1C at week 13 after randomization

  16. Changes A1C [ Time Frame: 15 weeks ]
    A1C value at Visit10 at 13 weeks after randomization minus A1C value at Visit 1 at week -2 (2 weeks before randomization)

  17. Proportion of A1C <7% at week 13 [ Time Frame: Week 13 ]
    the number of patients who have A1C <7% divided by the total number of patients who have A1C measurement at week 13 after randomization

  18. Proportion of A1C <8% at week 13 [ Time Frame: Week 13 ]
    the number of patients who have A1C <8% divided by the total number of patients who have A1C measurement at week 13 after randomization

  19. Mean basal insulin dose at week 13 [ Time Frame: Week 13 ]
    Average of basal insulin dose from patients' diary at week 13 after randomization

  20. Change in weight [ Time Frame: 15 weeks ]
    Weight difference between week 13 after randomization and baseline at week -2 (2 weeks before randomization) = weight at Visit 10 at week 13 - weight at Visit 1 at week -2.

  21. Change in waist circumference [ Time Frame: 15 weeks ]
    Waist circumference change between week 13 after randomization and baseline at week -2 (2 week before randomization)= waist circumference at Visit 10 at week 13- waist circumference at Visit 1 at week -2

  22. Change in carbohydrate intake [ Time Frame: 14 weeks ]
    Carbohydrate intake change between week 13 after randomization and baseline at week -1 = carbohydrate intake at Visit 10 at week 13 - carbohydrate intake at Visit 2 at week -1 (1 week before randomization)

  23. Proportion of patients who have A1C ≤ 7% with no hypoglycemia and no weight gain from baseline [ Time Frame: Week 13 ]
    the number of patients who have A1C ≤ 7% with no hypoglycemia and no weight gain from baseline divided by the total number of patients at Week 13 after randomization

  24. Proportion of patients who have A1C ≤ 7% with no hypoglycemia and weight gain <3% from baseline [ Time Frame: Week 13 ]
    the number of patients who have A1C ≤ 7% with no hypoglycemia and weight gain <3% from baseline divided by the total number of patients at Week 13 after randomization

  25. Proportion of patients who have fasting blood glucose ≤ 5.5 mmol/L without nocturnal hypoglycemia [ Time Frame: Week 13 ]
    the number of patients who have fasting blood glucose ≤ 5.5 mmol/L without nocturnal hypoglycemia divided by the total number of patients at Week 13 after randomization

  26. Change in DiabMedSat Score [ Time Frame: 14 weeks ]
    DiabMedSat Score will be generated using Diabetes Medication Satisfaction (DiabMedSat) questionnaire. It measures the levels of the subjects' satisfaction with their diabetes medication(s). The range of the score is 0 to 100. The higher the score, the greater the satisfaction. The changes in the score will measure the score difference between Visit 10 at week 13 after randomization and Visit 2 at week -1 (1 week before randomization)

  27. Change in HFS Score [ Time Frame: 14 weeks ]

    HFS Score will be measured by the Hypoglycemia Fear Survey which assesses the subject's behaviors to avoid hypoglycemia and to measure the subjects' worries about hypoglycemia and its consequences in the past 3 months. The range of the score will be 0 to 132. The higher the score, the greater the fear.

    The changes will be the score difference between Visit 10 at week 13 after randomization and Visit 2 at week -1 (1 week before randomization).


  28. HCP treatment satisfaction score [ Time Frame: Week 13 ]
    HCP treatment satisfaction score will be generated from Healthcare Provider treatment satisfaction questionnaire. It measures the levels of satisfaction of physicians in this study when prescribing this medication at Visit 10 at week 13 after randomization. The range is 0 to 15. The higher the score, the greater the satisfaction.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female adults with clinical diagnosis of T2DM diagnosed at least 1 year before screening and in stable health as assessed by investigator
  • Age between 18 and 80 years (inclusive)
  • Body mass index (BMI) between 20-40 kg/m2 (inclusive)
  • South Asian origin including Afghanistani, Bangladeshi, Indian, Nepali, Pakistani and Sri Lankan. This includes those patients who identify themselves as South Asian origin because their ancestors moved from South Asian to another country (e.g. Caribbean islands, Fiji, etc.)
  • A1C in range of 7.1-11% (inclusive)
  • Fasting glucose on self-monitoring of blood glucose (SMBG) or laboratory testing < 15 mmol/L within the last 30 days
  • Insulin naïve, uncontrolled on oral hypoglycemic medications
  • Kidney function assessment with eGFR >30 mL/min/1.73 m2
  • Written informed consent obtained

Exclusion Criteria:

  • History of insulin use (except emergency short-term use defined as less than 12 weeks for acute illness, hospitalization, pregnancy or with steroid use)
  • Use of GLP-1 receptor agonist in the past 3 months
  • Previous discontinuation of a GLP-1 receptor agonist due to safety, tolerability or lack of efficacy
  • Pregnant or anticipating pregnancy
  • Current use of steroid
  • Currently on any supervised, intensive, weight-loss dietary or exercise program
  • History of gastroparesis with moderate or higher severity
  • History of pancreatitis
  • Amylase and /or lipase more than three times the upper limit of normal or calcitonin ≥ 20 pg/mL (5.9 pmol/L)
  • Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN) syndrome
  • Allergic reaction to insulin secretagogues
  • History of weight loss surgery (bariatric bypass surgery or gastric banding)
  • Inability to check SMBG or wear CGM
  • History of severe liver disease or alcohol abuse
  • Severe hypoglycemic reaction (defined as third-party or ambulance assistance or emergency department visit) within the last 3 months before screening visit
  • Night-shift workers
  • Patients who are recommended to achieve relaxed targets of A1C up to 8.5% by Diabetes Canada 2018 clinical practice guidelines
  • Current enrollment in another intervention study
  • Patients who miss ≥1 injections of Basaglar/Lantus or discontinue the CGM device or can not record carbohydrate intake correctly during the run-in phase

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03819790


Contacts
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Contact: Harpreet Bajaj, MD, MPH 905-595-0560 harpreet.bajaj@lmc.ca
Contact: Karri Venn, RD 647-274-4133 karri.venn@LMC.ca

Locations
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Canada, Ontario
LMC Brampton Recruiting
Brampton, Ontario, Canada, L6S 0C9
Contact: Harpreet Bajaj, MBBS, MPH    905-595-0560    bramptonresearch@lmc.ca   
Sub-Investigator: Nupur Bahl, MD         
Sub-Investigator: Prakash Chandra, MD         
Sub-Investigator: Sanya Thobani, MD         
Sub-Investigator: Keerat Singh, CCPA         
LMC Etobicoke Recruiting
Etobicoke, Ontario, Canada
Contact: Hasnain Khandwala, MBBS    416-645-1035    etobicokeresearch@lmc.ca   
Sub-Investigator: Nadeen Aslam, MBBS         
Sub-Investigator: Jonathan Vecchiarelli, MD         
LMC Scarborough Recruiting
Toronto, Ontario, Canada, M1R 0B1
Contact: Jagjit Padda, MD    647-695-3866    scarboroughresearch@lmc.ca   
Sub-Investigator: Yuxi Chen, MD         
Sponsors and Collaborators
LMC Diabetes & Endocrinology Ltd.

Publications:

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Responsible Party: LMC Diabetes & Endocrinology Ltd.
ClinicalTrials.gov Identifier: NCT03819790     History of Changes
Other Study ID Numbers: VARIATION 2 SA
First Posted: January 29, 2019    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by LMC Diabetes & Endocrinology Ltd.:
Diabetes, type 2
GLP-1 RA
Insulin glargine
Glucose variability
Insulin Titration
South Asians

Additional relevant MeSH terms:
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Lixisenatide
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Insulin, Globin Zinc
Metformin
Insulin Glargine
Gliclazide
Hypoglycemic Agents
Physiological Effects of Drugs